scholarly journals Impaired responsiveness to B cell growth factor in a patient with common variable hypogammaglobulinemia

Blood ◽  
1985 ◽  
Vol 66 (2) ◽  
pp. 345-349 ◽  
Author(s):  
RT Perri ◽  
DJ Weisdorf
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
B Cells ◽  
Growth Factor ◽  
Cell Growth ◽  
B Cell ◽  
Immunoglobulin Synthesis ◽  
B Cell Growth Factor ◽  
Common Variable ◽  
Cell Defect

Abstract Common variable hypogammaglobulinemia (CVH) is a clinical syndrome that includes a diverse group of patients with heterogeneous defects resulting in impaired B cell proliferation and terminal differentiation into mature plasma cells capable of normal immunoglobulin synthesis and secretion. In this study, we report our identification of a previously undescribed intrinsic B cell defect in a patient with CVH. This patient's B cells showed a marked impairment in hemolytic plaque- forming cell (HePFC) formation compared with control B cells (15 v 80 HePFCs per culture, respectively). In addition, this patient's B cells displayed decreased B cell colony formation compared with control B cells (5 +/- 2 v 93 +/- 8, respectively). When examined for their responsiveness to phytohemagglutinin-T cell conditioned media (PHA- TCM), the patient's B cells displayed impaired B cell proliferation compared with control B cells (stimulation index [SI] 1.3 +/- 0.20 v 26 +/- 1.4 with 20% control PHA-TCM [vol/vol]). Impaired proliferation by the patient's B cells persisted with increasing concentrations of B cell growth factor (BCGF). Additionally, PHA-TCM prepared from the patient's T cells when compared with control PHA-TCM consistently showed less support for control B cell proliferation (SI 1.27 +/- 0.21 v 26 +/- 1.4, respectively). In coculture studies of B cell proliferation and immunoglobulin synthesis, patient's T cells showed no evidence of an enhanced suppressive effect or decreased helper effect. This patient's immune defects involve, first, an intrinsic B cell defect characterized by an impaired responsiveness to BCGF's proliferation signal and, second, impaired production of BCGF by the patient's T cells.

scholarly journals Impaired responsiveness to B cell growth factor in a patient with common variable hypogammaglobulinemia

Blood ◽  
1985 ◽  
Vol 66 (2) ◽  
pp. 345-349
Author(s):  
RT Perri ◽  
DJ Weisdorf
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
B Cells ◽  
Growth Factor ◽  
Cell Growth ◽  
B Cell ◽  
Immunoglobulin Synthesis ◽  
B Cell Growth Factor ◽  
Common Variable ◽  
Cell Defect

Common variable hypogammaglobulinemia (CVH) is a clinical syndrome that includes a diverse group of patients with heterogeneous defects resulting in impaired B cell proliferation and terminal differentiation into mature plasma cells capable of normal immunoglobulin synthesis and secretion. In this study, we report our identification of a previously undescribed intrinsic B cell defect in a patient with CVH. This patient's B cells showed a marked impairment in hemolytic plaque- forming cell (HePFC) formation compared with control B cells (15 v 80 HePFCs per culture, respectively). In addition, this patient's B cells displayed decreased B cell colony formation compared with control B cells (5 +/- 2 v 93 +/- 8, respectively). When examined for their responsiveness to phytohemagglutinin-T cell conditioned media (PHA- TCM), the patient's B cells displayed impaired B cell proliferation compared with control B cells (stimulation index [SI] 1.3 +/- 0.20 v 26 +/- 1.4 with 20% control PHA-TCM [vol/vol]). Impaired proliferation by the patient's B cells persisted with increasing concentrations of B cell growth factor (BCGF). Additionally, PHA-TCM prepared from the patient's T cells when compared with control PHA-TCM consistently showed less support for control B cell proliferation (SI 1.27 +/- 0.21 v 26 +/- 1.4, respectively). In coculture studies of B cell proliferation and immunoglobulin synthesis, patient's T cells showed no evidence of an enhanced suppressive effect or decreased helper effect. This patient's immune defects involve, first, an intrinsic B cell defect characterized by an impaired responsiveness to BCGF's proliferation signal and, second, impaired production of BCGF by the patient's T cells.

scholarly journals Production of B cell growth factor(s) by neoplastic B cells from hairy cell leukemia patients

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 573-577 ◽  
Author(s):  
RJ Ford ◽  
D Kwok ◽  
J Quesada ◽  
CG Sahasrabuddhe
Keyword(s):  
T Cells ◽  
B Cells ◽  
Growth Factor ◽  
Cell Growth ◽  
B Cell ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Human T Cells ◽  
B Cell Growth Factor ◽  
Normal Human

Abstract Recent studies have shown that normal human T cells contain a high- molecular-weight (mol wt) protein exhibiting B cell growth factor (BCGF) activity. Other studies have shown that virally transformed human B cells also secrete a high-mol-wt BCGF-like molecule in vitro. We have studied neoplastic B cells from patients with untreated hairy cell leukemia (HCL) to ascertain whether such cytoplasmic BCGF activity is present in the tumor cells. Studies on HCL cells from four patients indicated that BCGF-like activity was in fact present in the cytosolic extracts when tested on autochthonous HCL cells as well as on normal BCGF-dependent human B cell lines. Chromatographic analysis indicated that the BCGF activity from HCL cells was similar in mol wt as well as function to the normal T cell-derived cytosolic BCGF activity. These studies suggest that HCL cells contain and, in some cases, secrete a high-mol-wt growth factor that can be autostimulatory and appears to resemble a similar growth factor molecule found in normal human T cells.

scholarly journals Production of B cell growth factor(s) by neoplastic B cells from hairy cell leukemia patients

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 573-577
Author(s):  
RJ Ford ◽  
D Kwok ◽  
J Quesada ◽  
CG Sahasrabuddhe
Keyword(s):  
T Cells ◽  
B Cells ◽  
Growth Factor ◽  
Cell Growth ◽  
B Cell ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Human T Cells ◽  
B Cell Growth Factor ◽  
Normal Human

Recent studies have shown that normal human T cells contain a high- molecular-weight (mol wt) protein exhibiting B cell growth factor (BCGF) activity. Other studies have shown that virally transformed human B cells also secrete a high-mol-wt BCGF-like molecule in vitro. We have studied neoplastic B cells from patients with untreated hairy cell leukemia (HCL) to ascertain whether such cytoplasmic BCGF activity is present in the tumor cells. Studies on HCL cells from four patients indicated that BCGF-like activity was in fact present in the cytosolic extracts when tested on autochthonous HCL cells as well as on normal BCGF-dependent human B cell lines. Chromatographic analysis indicated that the BCGF activity from HCL cells was similar in mol wt as well as function to the normal T cell-derived cytosolic BCGF activity. These studies suggest that HCL cells contain and, in some cases, secrete a high-mol-wt growth factor that can be autostimulatory and appears to resemble a similar growth factor molecule found in normal human T cells.

scholarly journals Antigen-independent regulation of cytoplasmic calcium in B cells with a 12-kDa B-cell growth factor and anti-CD19.

1988 ◽  
Vol 85 (6) ◽  
pp. 1897-1901 ◽  
Author(s):  
J. A. Ledbetter ◽  
P. S. Rabinovitch ◽  
C. H. June ◽  
C. W. Song ◽  
E. A. Clark ◽  
...  
Keyword(s):  
B Cells ◽  
Growth Factor ◽  
Cell Growth ◽  
B Cell ◽  
Cytoplasmic Calcium ◽  
B Cell Growth Factor

Membrane depolarization of human B cells follows stimulation by either anti-μ or B-cell growth factor, but only anti-μ causes cell volume changes

1988 ◽  
Vol 21 (3) ◽  
pp. 155-164
Author(s):  
Wayne M. Yokoyama ◽  
Millie M. Chien ◽  
Susan E. Engardt ◽  
Susan W. Aguiar ◽  
Robert F. Ashman
Keyword(s):  
B Cells ◽  
Growth Factor ◽  
Cell Growth ◽  
B Cell ◽  
Cell Volume ◽  
Membrane Depolarization ◽  
Volume Changes ◽  
Human B Cells ◽  
B Cell Growth Factor

Abnormal response to a human B cell growth factor in patients with common variable immunodeficiency (CVI)

1991 ◽  
Vol 87 (6) ◽  
pp. 1138-1149 ◽  
Author(s):  
Julian L. Ambrus ◽  
Susan Haneiwich ◽  
Laura Chesky ◽  
Patrick McFarland ◽  
Marion G. Peters ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Growth ◽  
B Cell ◽  
Common Variable Immunodeficiency ◽  
Abnormal Response ◽  
B Cell Growth Factor ◽  
Common Variable ◽  
Human B Cell

scholarly journals Differential response of malignant human B-cells to anti-IgM immunoglobulin (anti-mu) and B-cell growth factor: unique direct cytotoxicity of anti-mu on prolymphocytic leukemia cells

Blood ◽  
1990 ◽  
Vol 76 (8) ◽  
pp. 1601-1606 ◽  
Author(s):  
CS Chan ◽  
F Soehnlen ◽  
GP Schechter
Keyword(s):  
B Cells ◽  
Growth Factor ◽  
Cell Growth ◽  
B Cell ◽  
Cell Cultures ◽  
Cell Subset ◽  
Thymidine Uptake ◽  
Prolymphocytic Leukemia ◽  
Direct Cytotoxicity ◽  
B Cell Growth Factor

Abstract We examined in vitro tritiated thymidine uptake by B cells from seven prolymphocytic leukemia (PLL), seven chronic lymphocytic leukemia (CLL), and four plasma cell leukemia (PCL) patients in response to culture with anti-human IgM antibody (anti-mu) and B-cell growth factor (BCGF). In contrast to the stimulatory effect observed in normal B-cell cultures, the divalent F(ab')2 anti-mu antibody uniquely inhibited the autonomous proliferation and induced marked cytotoxicity in six of seven PLL cell cultures independent of complement or Fc-receptor- mediated mechanisms. There was neither stimulation or inhibition of the slgM+ CLL or the slgM- PCL cells. The inhibitory effect on the PLL cells was observed at an anti-mu concentration below the stimulatory threshold for normal B cells. Significant impairment of trypan blue exclusion was delayed until 48 hours, with morphological cellular changes suggestive of a programmed cell death mechanism or apoptosis. The cytotoxicity was independent of the slgM-staining intensity or the autonomous and BCGF-augmented DNA synthetic activity of the PLL cells and was similar in patients with de novo PLL or with prolymphocytic transformation of CLL. Cells from a PLL patient were separated by elutriation into two fractions, a BCGF-unresponsive large “transformed” cell fraction with marked autonomous DNA synthesis and a smaller lymphoid cell subset with low 3H-thymidine uptake that could be augmented by BCGF. Both fractions were equally susceptible to the cytotoxic effect of anti-mu. These data suggest that certain slgM- bearing malignant B cells are susceptible to anti-mu-triggered cytotoxicity. They may represent the malignant counterpart of a “tolerogenic” normal B-cell subset, and the unique direct cytotoxicity of anti-mu may provide a therapeutic strategy specifically for PLL.

scholarly journals Purification to homogeneity of a high molecular weight human B cell growth factor; demonstration of specific binding to activated B cells; and development of a monoclonal antibody to the factor.

1985 ◽  
Vol 162 (4) ◽  
pp. 1319-1335 ◽  
Author(s):  
J L Ambrus ◽  
C H Jurgensen ◽  
E J Brown ◽  
A S Fauci
Keyword(s):  
Molecular Weight ◽  
Monoclonal Antibody ◽  
B Cells ◽  
Growth Factor ◽  
Cell Growth ◽  
B Cell ◽  
High Molecular Weight ◽  
Sodium Dodecyl ◽  
Western Blots ◽  
B Cell Growth Factor

High molecular weight B cell growth factor (HMW-BCGF) produced by a T cell line was purified to homogeneity and demonstrated to bind specifically to activated human B cells. A monoclonal antibody to HMW-BCGF was developed that (a) specifically inhibited the activity of HMW-BCGF in enhancing B cell proliferation, (b) specifically bound to HMW-BCGF in Western blots, (c) specifically absorbed HMW-BCGF activity from culture supernatants, and (d) specifically absorbed an internally labeled protein from T-ALL supernatant which comigrates with HMW-BCGF on sodium dodecyl sulfate-polyacrylamide gels. This antibody should help in cloning the gene for HMW-BCGF and further exploring the physiologic roles of HMW-BCGF.

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