scholarly journals The requirement for adherent cells in the Fc fragment-induced proliferative response of murine spleen cells.

1979 ◽  
Vol 150 (2) ◽  
pp. 256-266 ◽  
Author(s):  
E L Morgan ◽  
W O Weigle
Keyword(s):  
Cell Proliferation ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Population ◽  
Proliferative Response ◽  
Adherent Cell ◽  
Adherent Cells ◽  
Spleen Cells ◽  
Murine Spleen

The proliferative response of mouse B lymphocytes induced by Fc fragments was found to be dependent upon an adherent cell population. The adherent cell is esterase positive, irradiation resistant, and not susceptible to lysis by anti-thymus serum and complement. The mechanism(s) by which Fc fragments induce B-cell proliferation could be the result of the interaction of Fc with both B cells and adherent cells or with adherent cells which then release factors that trigger the B cells to proliferate. Spleen cells from the C3H/HeJ mouse were shown to be unable to respond to Fc fragments. The addition of adherent cells from either C3H/St or C3H/HeN mice to adherent cell depleted C3H/HeJ cells enabled them to respond to Fc, indicating the defect was in the adherent cell population.

scholarly journals Regulation of Fc fragment-induced murine spleen cell proliferation.

1980 ◽  
Vol 151 (1) ◽  
pp. 1-11 ◽  
Author(s):  
E L Morgan ◽  
W O Weigle
Keyword(s):  
Cell Proliferation ◽  
Spleen Cell ◽  
Proliferative Response ◽  
Cleavage Product ◽  
Adherent Cell ◽  
Adherent Cells ◽  
Splenic Lymphocytes ◽  
Cell Type ◽  
Fc Fragment ◽  
Murine Spleen

Murine splenic lymphocytes proliferate in response to supernatant material derived from Fc fragment-pulsed splenic adherent cells. The stimulatory supernatant results from the interaction of Fc fragments with adherent cells or adherent cell supernate. Isolation of the stimulatory material in the supernate by Sephadex chromatography revealed that the mitogenic component was a cleavage product of Fc with a mol wt of approximately 14,000. The spleen cell type responsible for the generation of mitogenic Fc subfragments appears to be a macrophage. Unstimulated macrophages release an active supernate without being exposed to Fc fragments. The supernate of unstimulated macrophages apparently contain an enzyme which is capable of cleaving Fc fragments into the 14,000-mol wt mitogenic molecules. The spleen cell population induced to proliferate in response to the adherent cell supernate is present in T-cell depleted and Sephadex G-10 filtered cell preparations. Depletion of cells bearing immunoglobulin on their surfaces results in a reduced proliferative response to the mitogenic supernatant material indicating that it is probably a B cell.

scholarly journals In vitro tolerance induction of neonatal murine B cells.

1976 ◽  
Vol 143 (6) ◽  
pp. 1327-1340 ◽  
Author(s):  
E S Metcalf ◽  
N R Klinman
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Specific Interaction ◽  
Tolerance Induction ◽  
Antigen Receptors ◽  
Spleen Cells ◽  
Protein Conjugates ◽  
Immature B Cells

The susceptibility of neonatal and adult B lymphocytes to tolerance induction was analyzed by a modification of the in vitro splenic focus technique. This technique permits stimulation of individual hapten-specific clonal precursor cells from both neonatal and adult donors. Neonatal or adult BALB/c spleen cells were adoptively transferred into irradiated, syngeneic, adult recipients which had been carrier-primed to hemocyanin (Hy), thus maximizing stimulation to the hapten 2,4-dinitrophenyl coupled by Hy (DNP-Hy). Cultures were initially treated with DNP on several heterologous (non-Hy) carriers and subsequently stimulated with DNP-Hy. Whereas the responsiveness of adult B cells was not diminished by pretreatment with any DNP conjugate, the majority of the neonatal B-cell response was abolished by in vitro culture with all of the DNP-protein conjugates. During the 1st wk of life, the ability to tolerize neonatal splenic B cells progressively decreased. Thus, tolerance in this system is: (a) restricted to B cells early in development; (b) established by both tolerogens and immunogens; (c) achieved at low (10(-9) M determinant) antigen concentrations; and (d) highly specific, discriminating between DNP- and TNP-specific B cells. We conclude that: (a) B lymphocytes, during their development, mature through a stage in which they are extremely susceptible to tolerogenesis; (b) the specific interaction of B-cell antigen receptors with multivalent antigens, while irrelevant to mature B cells, is tolerogenic to neonatal (immature) B cells unless antigen is concomitantly recognized by primed T cells; and (c) differences in the susceptibility of immature and mature B lymphocytes to tolerance induction suggest intrinsic differences between neonatal and adult B cells and may provide a physiologically relevant model for the study of tolerance to self-antigens.

scholarly journals Activated B cells express receptors for, and proliferate in response to, pure interleukin 2.

1984 ◽  
Vol 160 (4) ◽  
pp. 1170-1183 ◽  
Author(s):  
R H Zubler ◽  
J W Lowenthal ◽  
F Erard ◽  
N Hashimoto ◽  
R Devos ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Interleukin 2 ◽  
T Helper ◽  
Spleen Cells ◽  
Human Spleen ◽  
Apparent Dissociation Constant ◽  
Activated B Cells

In this study we investigated whether interleukin 2 (IL-2) acts on B cell proliferation and whether activated B cells express IL-2 receptors. First, the functional activity of immunoaffinity-purified or recombinant human IL-2 was studied in a B blast assay using positively selected murine surface Ig-positive cells that had been activated by lipopolysaccharide (LPS) plus anti-Ig antibodies (anti-Ig). In this assay, T cells were not detected by fluorescence-activated cell sorter analysis. It was found that both IL-2 preparations led to optimal B cell proliferation compared with supernatants obtained from murine or human spleen cells or murine cloned T helper cells. Second, we observed that the IL-2 requirement in this assay was about the same as in a proliferation assay using lectin-activated polyclonal murine Lyt-2-positive T cells. Third, analysis of the binding of radiolabeled immunoaffinity-purified IL-2 to B cells indicated that LPS plus anti-Ig-activated B cells expressed a mean of 3,500 IL-2 receptors per cell with an apparent dissociation constant of 150 pM. However, neither nonactivated B cells nor B cells activated by LPS alone exhibited significant specific IL-2 binding. The functional and the receptor data are consistent with the conclusion that IL-2 is a growth factor not only for T cells but also for B cells.

CD19+,CD27+, IgM+ B Cells of Patients with Persistent Polyclonal B Cell (PPBL) Proliferate in a Low Intensity CD40-CD154 Interaction and Show Evidence of Immunoglobulin Isotype Switching

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4920-4920
Author(s):  
Robert Delage ◽  
Emmanuelle Dugas-Bourdages ◽  
Annie Roy ◽  
Sonia Neron ◽  
Andre Darveau
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Population ◽  
Genetic Defect ◽  
Memory B Cells ◽  
Isotype Switching ◽  
Low Intensity

Abstract Persistent polyclonal B cell lymphocytosis (PPBL) is a rare disorder characterized by an expansion of memory B cells CD19+, CD27+, IgM+. PPBL occurs mainly in female, is associated with HLA DR7, an increased level of serum IgM and the lymphocytes frequently show a bi-nucleated morphology. The patients have in most cases smoking habits and the clinical evolution is usually benign but we have previously described one case of lymphoma 19 years after a diagnosis of PPBL. Although the pathophysiology remains unknown, a familial occurrence is at the basis of this disorder suggesting a genetic defect. Moreover, multiple bcl-2\Ig gene rearrangements are present in all patients and an extra isochromosome 3 (i3)(q10) is frequently shown in the B cell population. The binding of CD40 to CD154 expressed on activated T cells plays a central role in B cell activation, proliferation and Ig isotype switching. We have previously shown that PPBL B lymphocytes were unable to respond to the proliferative signal delivered in vitro by CD40 in the CD40-CD154 system, indicating a possible defect in the CD40 pathway although CD40 expression, sequencing and tyrosine phosphorylation appeared normal. However, it has been shown recently that a reduced intensity of CD40-CD154 interaction in the presence of IL-2, IL-4 and IL-10 results in the proliferation, expansion and immunoglobulin secretion of normal memory CD19+,CD27+, IgM+ B cells. PPBL B lymphocytes sharing the same phenotype as normal memory B cells, we design a study to investigate the response of B lymphocytes from patient with PPBL in culture in high and low CD154 interaction. Proliferation and flow cytometry analysis of B lymphocytes from 6 patients with PPBL were closely monitored through a 14 day culture period and the Ig secretion was determined by Elisa. Our results show that a low intensity CD40- CD154 interaction in the presence of IL-2, IL-4 and IL-10 induces proliferation of the CD19+,CD27+,IgM+ PPBL population 6 to 20 times higher compared to high CD154 interaction. Interestingly, the CD19+, IgG+ cell population that constitutes less than 5% of the cell population at the beginning of the culture, increased over 25% on day 14. As for normal controls, we observed the emergence of a CD19+,CD27− cell population and the disappearance of surface IgD. Culture of B cells from patients with PPBL resulted in high Ig secretion. Moreover on day 14, Ig isotype analysis showed higher IgG levels compared to IgM. We conclude that PPBL B lymphocytes could proliferate in the CD40- CD154 system under proper condition and that proliferation also results in IgM and IgG secretion indicating an adequate CD40 signalling pathway. Moreover, this report provides the first evidence of in vitro Ig isotype switching of CD19+,CD27+,IgM+ B lymphocytes from PPBL. These results also suggest a possible defect in the interaction with T cells as observed in the hyper-IgM syndrome or alternatively, other cells from the microenvironment.

Effects of c-Src Overexpression in CD40-Activated Human B Lymphocytes.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3868-3868
Author(s):  
Daniel Jung ◽  
Marie-Pierre Cayer ◽  
Maryse Proulx ◽  
Xue-Zhong Ma ◽  
Darinka Sakac ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Expansion ◽  
Kinase Activity ◽  
Dominant Negative ◽  
Human B Cells ◽  
Normal Human ◽  
Transcriptional Pathway

Abstract The 60-kDa c-Src is the normal human cellular protein counterpart of the highly transforming v-src gene. Recently, c-Src activity was reported to increase in CD40-activated human B cells in the presence of IL-4, suggesting its involvement in proliferation. We report here that c-Src expression is detectable concomitant with the detection of Stat5b and, therefore, Stat5b may serve as a substrate for tyrosine phosphorylation by c-Src, inducing the activation of Stat5b and initiating a transcriptional pathway important for B cell expansion. To elucidate the exact role of c-Src in the proliferation of normal B cells, we undertook c-Src over-expression experiments. Recombinant adenoviruses Ad5/F35 vectors, which we previously reported as highly efficient for B cell transduction, encoding wild-type c-Src(c-Src/WT), constitutively active c-Src(c-Src/CA), dominant negative c-Src(c-Src/DN) or EYFP were constructed. B lymphocytes purified from human peripheral blood were activated with soluble CD154 in the presence or absence of IL-2, IL-4 and IL-10, and infected with the viruses. Real-time PCR and Western blot analysis revealed that vector-transferred c-Src were strongly expressed in infected B cells as early as 48 hours post infection. Kinase assays confirmed that vector-transferred c-Src/WT and c-Src/CA display a strong kinase activity whereas negligible kinase activity was detected with Ad5/F35-c-Src/DN. No significant variation of B cell expansion could be observed between uninfected cells, Ad/F35-EYFP and Ad5/F35-c-Src/CA or Ad5/F35-c-Src/WT infected cells, suggesting that B cell proliferation induced by endogenous c-Src already attains a maximum rate of expansion, which cannot be further enhanced by supplemental exogenous c-Src. In contrast, overexpression of c-Src/DN results in a 40% inhibition of B cell expansion. These results suggest that transgenic dominant negative c-Src may compete with endogenous c-Src resulting in a partial inhibition of a transcriptional pathway involved in B cell proliferation. In conclusion, our results confirm an important role for c-Src in the expansion of normal human B cells in vitro.

Constitutive Baff Signalling Plays a Key Role in CLL Development by Promoting Tumor Cell Survival

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 28-28
Author(s):  
Thomas Enzler ◽  
Weizhou Zhang ◽  
Arnon P. Kater ◽  
George F. Widhopf ◽  
Carlo M. Croce ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
B Cells ◽  
B Cell ◽  
Cell Survival ◽  
Cell Population ◽  
Lymphoproliferative Disease ◽  
Leukemia Cells ◽  
Nuclear Antigen ◽  
Terminal Deoxynucleotidyl Transferase ◽  
B Cell Survival

Abstract The B cell-activating factor of the tumor necrosis factor family (BAFF) is a potent B-cell survival factor. We recently found that nurselike cells, which presumably reside in the leukemia-microenvironment, express BAFF, which promotes survival of leukemia cells of patients with chronic lymphocytic leukemia (CLL) cells through activation of the classical NF-kB pathway. To study the influence of BAFF on leukemogenesis, we crossed BAFF transgenic (Tg) mice with either Eμ-TCL-Tg mice, which develop a lymphoproliferative disease resembling human CLL at about 12 months of age, or Ea-MYC-Tg mice, which experience higher rates of apoptosis in their mature B cells, but do not develop overt lymphoproliferative disease per se. We found that BAFF/TCL1-Tg mice had a shorter mean survival than either TCL1-Tg or BAFF-Tg mice due to the early development of a CD5+CD3−CD45Rlo leukemia B-cell population resembling human CLL at the age of about 3–4 months as compared to 7–9 months in TCL1-Tg mice. In contrast none of the BAFF-Tg or wt mice developed lymphoproliferative disease over the 26-month period of observation. The CD5+CD3−CD45Rlo cell population increased in BAFF/TCL1-Tg mice relatively rapidly, coming to represent >99% of the total blood mononuclear cells of 9-month-old double Tg animals. At this age, these mice also developed massive splenomegaly and their spleens were heavily infiltrated with leukemia B cells. Southern blot analyses of splenocytes harvested at various ages detected oligoclonal/monoclonal splenic B cell populations at approximately 4 months of age in the BAFF/TCL1-Tg mice compared to 9–12 months in the TCL1-Tg mice. Similarly, Ea-MYC-Tg mice, generated by inserting a single copy of MYC into the mouse Ig heavy-chain Ca locus, were crossed with the BAFF-Tg mice in order to obtain BAFF/MYC-Tg mice. In contrast to Ea-MYC-Tg mice, the BAFF/MYC-Tg mice developed expansions of CD5+CD3−CD45Rlo CLL-like leukemia B cells in the blood and spleen starting at 4 months of age, resulting in splenomegaly. These cells could be adoptively transferred into syngeneic BAFF-Tg mice, allowing for continued proliferation of such CD5+CD3−CD45Rlo leukemia B-cells and development lymphoproliferative disease. Staining of splenic sections for proliferating-cell nuclear antigen (PCNA) demonstrated similar high-rates of cell-proliferation in Ea-MYC-Tg mice and BAFF/MYC-Tg mice, which were twice greater than those of BAFF-Tg mice or wt mice. In contrast, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) of splenic sections revealed that Ea-MYC-Tg mice had 4 times greater proportions of apoptotic splenocytes than did BAFF/MYC-Tg mice, suggesting that BAFF promoted B cell expansion by inhibiting B cell turnover. Consistent with this, we found that BAFF induced in TCL1-Tg, as well as MYC-Tg mice, high-level B cell expression of anti-apoptotic proteins such as Bcl-XL, Bcl-2, A1/Bfl1, and Pim-2 in leukemia B cells. Also, these leukemia B cells transferred more efficiently into syngeneic BAFF-Tg mice than in mice lacking expression of BAFF. We treated BAFF-Tg mice with intraperitoneal (i.p.) injections of BAFF-neutralizing BR3-Fc or control protein prior to adoptive transfer of leukemia cells of Eμ-TCL1-Tg mice. We found that i.p. injection of 200 mg BR3-Fc into the recipient animals reduced the numbers of circulating CLL cells relative to that found in control-treated mice by nearly 20% (18.2%±5.3%; n=3) within 6 days. These findings indicate that BAFF accelerates development of leukemia in Eμ-TCL1-Tg and Ea-MYC-Tg mice primarily by enhancing leukemia B-cell survival, but not leukemia-cell proliferation, resulting in accelerated rates of tumor development and apparent enhancement of leukemia B cell proliferation in vivo. These findings suggest that targeting BAFF or BAFF-expressing cells within the leukemia microenvironment might be an effective strategy for treatment of CLL and related B-cell malignancies.

scholarly journals Impaired expression of cell surface receptors for B cell growth factor by chronic lymphocytic leukemia B cells

Blood ◽  
1986 ◽  
Vol 67 (4) ◽  
pp. 943-948 ◽  
Author(s):  
RT Perri
Keyword(s):  
Cell Proliferation ◽  
B Cells ◽  
Growth Factor ◽  
Cell Surface ◽  
B Cell ◽  
Proliferative Response ◽  
Lymphocytic Leukemia ◽  
Cell Surface Receptors ◽  
Surface Receptors ◽  
B Cell Growth Factor

Abstract Normal human B cell proliferation is controlled by various immunoregulatory signals including the T cell-derived lymphokine B cell growth factor (BCGF). The role of BCGF in the regulation of malignant B cell proliferation is unclear. Therefore, we studied the proliferative response of purified chronic lymphocytic leukemia (CLL) B cells to BCGF. For all CLL patients studied, CLL B cells showed a decreased proliferative response as compared with control B cells for BCGF- induced B cell proliferation (patient 291 +/- 59 cpm v control 3,942 +/- 622, mean +/- SEM). This impaired proliferative response appeared to be intrinsic to CLL B cells since it was not corrected by incubation with increasing concentrations of BCGF. Attainment of normal B cell responsiveness to BCGF requires the processing of an initial activation signal which results in the expression of cell surface receptors for BCGF. Increasing concentrations of the B cell activation signal (the F(ab')2 fragment of goat anti-human mu chain) did not improve CLL B cell responsiveness to BCGF. Three-day activated CLL B cells compared with activated control B cells demonstrated a marked impairment in their ability to absorb out the BCGF activity present in the BCGF preparation (BCGF activity absorbed out, patient 12.8% v control 53%). Pretreatment of CLL B cells with neuraminidase failed to improve either the proliferative response to BCGF or the expression of cell surface receptors for BCGF by the CLL B cells. This study suggests that the impaired responsiveness to BCGF by CLL B cells is the result of impaired expression of cell surface receptors for BCGF when CLL B cells are exposed to activation signals.

scholarly journals Major histocompatibility complex-restricted self-recognition in responses to trinitrophenyl-ficoll. Adaptive differentiation and self-recognition by B cells.

1982 ◽  
Vol 156 (5) ◽  
pp. 1415-1434 ◽  
Author(s):  
A Singer ◽  
R J Hodes
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Population ◽  
Normal Strain ◽  
Spleen Cells ◽  
Host Environment ◽  
Self Recognition ◽  
Accessory Cells

The present study has examined the possibility of TNP-Ficoll-responsive B cells recognize the MHC determinants expressed by the accessory cells with which they interact for the generation of T cell-independent responses to "high" concentrations (10(-2) micrograms/ml) of TNP-Ficoll. In experiments with B cells from normal mice, it was found that MHC homology between the TNP-Ficoll-responsive B cells and accessory cells was not required. Nevertheless, TNP-Ficoll-responsive B cells from both fully allogeneic (A leads to B) and F1 leads to parent radiation bone marrow chimeras were triggered by accessory cells expressing host-type, but not uniquely donor-type, MHC determinants. The MHC gene products responsible for this apparent B cell-accessory restriction were encoded in the left side, i.e., the K and/or I-A region, of H-2. Such genetic restrictions were shown not to be imposed by the residual T cells contaminating the chimeric B cell populations because T cell reconstitution experiments using "unrestricted" F1 T cells from normal mice did not fully overcome the marked preference of the chimeric B cells for accessory cells expressing appropriate (host-type) MHC determinants. To directly determine whether TNP-Ficoll-responsive B cells from fully allogeneic chimeras are unable to recognize and cooperate with syngeneic strain A accessory cells, unfractionated spleen cells from A leads to B chimeras are co-cultured with unfractionated spleen cells from essentially syngeneic normal strain A mice. In such co-cultures, all the accessory cells express strain A MHC determinants, and all T cell requirements would be fulfilled by the T cells present in the normal strain A spleen cell population. After stimulation of the co-cultures with TNP-Ficoll, it was found that virtually all the PFC that had been generated in the co-cultures were derived from the normal B cell population, and essentially none were derived from the chimeric A leads to B B cell population. The failure of the chimeric B cells to be activated in such co-cultures was specifically due to their maturation in a fully allogeneic host environment because TNP-Ficoll-responsive B cells from A leads to (A X B) F1 chimeric mice were successfully triggered in co-cultures with normal spleen cells. These experiments demonstrated that the co-culture conditions did fulfill the MHC restriction requirements for activating TNP-Ficoll-responsive strain A B cells that had matured in a syngeneic or semi-syngeneic differentiation environment, but did not fulfill the MHC restriction requirements for activating TNP-Ficoll-responsive strain A B cells that had matured in a fully allogeneic differentiation environment. Taken together, these results demonstrate that (a) TNP-Ficoll-responsive B cells recognize the MHC determinants expressed by accessory cells, and (b) their MHC specificity is influenced by the MHC haplotype of the host environment in which the B cells had differentiated.

Pulmonary B Lymphocytes Ameliorate Alzheimer's Disease-Like Neuropathology

2021 ◽  
Author(s):  
Weixi Feng ◽  
Yanli Zhang ◽  
Tianqi Wang ◽  
Qian Li ◽  
Ze Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Proliferation ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Brain Parenchyma ◽  
Amyloid Aβ ◽  
5Xfad Mice ◽  
The Brain

Abstract Increasing evidences reveal that the peripheral immune system is involved in the pathogenesis of Alzheimer's disease (AD). Here, we report that pulmonary B lymphocytes mitigate beta-Amyloid (Aβ) pathology in 5xFAD mice. The proportion of B cells, rather than T cells, increases within the brain, meningeal and lung tissues in 3-month-old 5xFAD mice. Deletion of mature B cells aggravates Aβ load and memory deficits of 5xFAD mice. Mechanistically, pulmonary B cells can migrate to the brain parenchyma and produce interleukin-35, which inhibits neuronal β-site APP-cleaving enzyme 1 expression, and subsequently reduces the production of Aβ. In turn, pulmonary B cell proliferation is associated with activation of the toll-like receptor/nuclear factor kappa-B pathway through elevated Aβ that is drained from the brain parenchyma to the lungs via meningeal lymphatics. Furthermore, promoting pulmonary B cell proliferation via overexpression of B-cell-activating factor ameliorates brain Aβ load and improves cognitive functions of 10-month-old 5xFAD mice. Together, these results highlight the lungs as both immune targets and effector organs in Aβ pathogenesis. Pulmonary B cells could serve as a potential target against AD.

scholarly journals Impaired expression of cell surface receptors for B cell growth factor by chronic lymphocytic leukemia B cells

Blood ◽  
1986 ◽  
Vol 67 (4) ◽  
pp. 943-948 ◽  
Author(s):  
RT Perri
Keyword(s):  
Cell Proliferation ◽  
B Cells ◽  
Growth Factor ◽  
Cell Surface ◽  
B Cell ◽  
Proliferative Response ◽  
Lymphocytic Leukemia ◽  
Cell Surface Receptors ◽  
Surface Receptors ◽  
B Cell Growth Factor

Normal human B cell proliferation is controlled by various immunoregulatory signals including the T cell-derived lymphokine B cell growth factor (BCGF). The role of BCGF in the regulation of malignant B cell proliferation is unclear. Therefore, we studied the proliferative response of purified chronic lymphocytic leukemia (CLL) B cells to BCGF. For all CLL patients studied, CLL B cells showed a decreased proliferative response as compared with control B cells for BCGF- induced B cell proliferation (patient 291 +/- 59 cpm v control 3,942 +/- 622, mean +/- SEM). This impaired proliferative response appeared to be intrinsic to CLL B cells since it was not corrected by incubation with increasing concentrations of BCGF. Attainment of normal B cell responsiveness to BCGF requires the processing of an initial activation signal which results in the expression of cell surface receptors for BCGF. Increasing concentrations of the B cell activation signal (the F(ab')2 fragment of goat anti-human mu chain) did not improve CLL B cell responsiveness to BCGF. Three-day activated CLL B cells compared with activated control B cells demonstrated a marked impairment in their ability to absorb out the BCGF activity present in the BCGF preparation (BCGF activity absorbed out, patient 12.8% v control 53%). Pretreatment of CLL B cells with neuraminidase failed to improve either the proliferative response to BCGF or the expression of cell surface receptors for BCGF by the CLL B cells. This study suggests that the impaired responsiveness to BCGF by CLL B cells is the result of impaired expression of cell surface receptors for BCGF when CLL B cells are exposed to activation signals.

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