ICOS Gene Polymorphisms In B-Cell Chronic Lymphocytic Leukemia In a Polish Population.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4614-4614 ◽  
Author(s):  
Irena Frydecka ◽  
Lidia Karabon ◽  
Anna Jedynak ◽  
Anna Tomkiewicz ◽  
Edyta Pawlak ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Costimulatory Molecule ◽  
Interleukin 2 ◽  
Lymphocytic Leukemia ◽  
Polish Population ◽  
Increased Risk ◽  
Cell Chronic Lymphocytic Leukemia

Abstract Abstract 4614 Introduction: There is strong evidence that altered immunological function entails an increased risk of B-cell chronic lymphocytic leukemia (B-CLL). The main mechanism of an antitumor response depends on T-cell activation. Unlike the constitutively expressed CD28, inducible costimulatory molecule (ICOS) is expressed on the T-cell surface after activation. ICOS enhances all the basic T-cell responses to a foreign antigen, namely proliferation, secretion of lymphokines, the up-regulation of molecules that mediate cell-cell interaction, and effective help for antibody secretion by B cells. ICOS is essential for both efficient interaction between T and B cells and normal antibody responses to T cell-dependent antigens. It does not up-regulate the production of interleukin-2, but superinduces the synthesis of interleukin-10. Our previous results indicated a role of ICOS gene as a susceptibility locus to B-CLL. Therefore an extended study was undertaken to evaluate the association between four ICOS polymorphisms (which were recently described as functional ones) and susceptibility to B-CLL in a Polish population. Methods: A case-control study of 296 individuals including 146 B-CLL patients was conducted on four polymorphisms in the ICOS gene. Genotyping of the polymorphisms ICOSISV1+173T>C (rs10932029), ICOSc.1624C>T (rs10932037), ICOSc.2373G>C (rs4675379), and ICOSc.602A>C (rs10183087) was done using allelic discrimination methods with the TaqManÒ SNP Genotyping Assay. Results: There were no statistically significant differences in the allele, genotype, and haplotype distributions between B-CLL patients and healthy controls for any of the investigated polymorphic markers in the ICOS gene. However, we noted that patients carrying genotype ISV1+173T>C [TT], ICOSc.602A>C [AA], ICOSc.1624C>T [CC], and ICOSc.2373G>C [GG] have a decreased frequency of progression to a higher Rai stage during 60-month follow-up (21.35 vs. 40.8%, p=0.013) compared with other individuals. Conclusion: This study showed that the investigated polymorphisms do not modulate the risk of B-CLL in the Polish population, but are associated with disease dynamics in particular with the time to Rai stage progression. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Defective T cell-mediated, isotype-specific immunoglobulin regulation in B cell chronic lymphocytic leukemia

Blood ◽  
1988 ◽  
Vol 71 (4) ◽  
pp. 1012-1020 ◽  
Author(s):  
JS Moore ◽  
MB Prystowsky ◽  
RG Hoover ◽  
EC Besa ◽  
PC Nowell
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Cell Activity ◽  
Lymphocytic Leukemia ◽  
Specific Immunoglobulin ◽  
Cell Chronic Lymphocytic Leukemia

The consistent occurrence of T cell abnormalities in patients with B cell chronic lymphocytic leukemia (B-CLL) suggest that the non- neoplastic host T cells may be involved in the pathogenesis of this B cell neoplasm. Because potential defects of immunoglobulin regulation are evident in B-CLL patients, we investigated one aspect of this by studying the T cell-mediated immunoglobulin isotype-specific immunoregulatory circuit in B-CLL. The existence of class-specific immunoglobulin regulatory mechanisms mediated by Fc receptor-bearing T cells (FcR + T) through soluble immunoglobulin binding factors (IgBFs) has been well established in many experimental systems. IgBFs can both suppress and enhance B cell activity in an isotype-specific manner. We investigated the apparently abnormal IgA regulation in a B-CLL patient (CLL249) whose B cells secrete primarily IgA in vitro. Enumeration of FcR + T cells showed a disproportionate increase in IgA FcR + T cells in the peripheral blood of this patient. Our studies showed that the neoplastic B cells were not intrinsically unresponsive to the suppressing component of IgABF produced from normal T cells, but rather the IgABF produced by the CLL249 host T cells was defective. CLL249 IgABF was unable to suppress IgA secretion by host or normal B cells and enhanced the in vitro proliferation of the host B cells. Size fractionation of both normal and CLL249 IgABF by gel-filtration high- performance liquid chromatography (HPLC) demonstrated differences in the ultraviolet-absorbing components of IgABF obtained from normal T cells v that from our patient with defective IgA regulation. Such T cell dysfunction may not be restricted to IgA regulation, since we have found similar expansion of isotype-specific FcR + T cells associated with expansion of the corresponding B cell clone in other patients with B-CLL. These data suggest that this T cell-mediated regulatory circuit could be significantly involved in the pathogenesis of B-CLL.

Leukemia-associated monoclonal and oligoclonal TCR-BV use in patients with B-cell chronic lymphocytic leukemia

Blood ◽  
2003 ◽  
Vol 101 (3) ◽  
pp. 1063-1070 ◽  
Author(s):  
Mohammad-Reza Rezvany ◽  
Mahmood Jeddi-Tehrani ◽  
Hans Wigzell ◽  
Anders Österborg ◽  
Håkan Mellstedt
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Cd8 T Cells ◽  
Leukemia Cell ◽  
Lymphocytic Leukemia ◽  
Cell Chronic Lymphocytic Leukemia

Abstract T-cell receptor–B-variable (TCR-BV) gene usage and the CDR3 size distribution pattern were analyzed by reverse transcription–polymerase chain reaction (RT-PCR) in patients with B-cell chronic lymphocytic leukemia (B-CLL) to assess the T-cell repertoire. The use of TCR-BV families in CD4 and CD8 T cells stimulated with autologous activated leukemic cells was compared with that of freshly obtained blood T cells. Overexpression of individual TCR-BV families was found in freshly isolated CD4 and CD8 T cells. Polyclonal, oligoclonal, and monoclonal TCR-CDR3 patterns were seen within such overexpressed native CD4 and CD8 TCR-BV families. In nonoverexpressed TCR-BV families, monoclonal and oligoclonal populations were noted only within the CD8 subset. After in vitro stimulation of T cells with autologous leukemic B cells, analyses of the CDR3 length patterns showed that in expanded TCR-BV populations, polyclonal patterns frequently shifted toward a monoclonal/oligoclonal profile, whereas largely monoclonal patterns in native overexpressed TCR-BV subsets remained monoclonal. Seventy-five percent of CD8 expansions found in freshly obtained CD8 T cells further expanded on in vitro stimulation with autologous leukemic B cells. This suggests a memory status of such cells. In contrast, the unusually high frequency of CD4 T-cell expansions found in freshly isolated peripheral blood cells did not correlate positively to in vitro stimulation as only 1 of 9 expansions continued to expand. Our data suggest that leukemia cell–specific memory CD4 and CD8 T cells are present in vivo of patients with CLL and that several leukemia cell–associated antigens/epitopes are recognized by the patients' immune system, indicating that whole leukemia cells might be of preference for vaccine development.

scholarly journals Defective helper function of purified T4 cells and excessive suppressor activity of purified T8 cells in patients with B-cell chronic lymphocytic leukemia. T4 suppressor effector cells are present in certain patients

Blood ◽  
1988 ◽  
Vol 71 (6) ◽  
pp. 1551-1560
Author(s):  
JE Kunicka ◽  
CD Platsoucas
Keyword(s):  
T Cell ◽  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Lymphocytic Leukemia ◽  
Pokeweed Mitogen ◽  
Suppressor Activity ◽  
Effector Cells ◽  
Helper Function ◽  
Cell Chronic Lymphocytic Leukemia

We investigated helper and suppressor functions to B-cell responses and T-T cell interactions of purified T4 and T8 cells from 20 untreated patients with B-cell chronic lymphocytic leukemia (CLL). Appropriate mixtures of purified T4 or T8 cells from patients with CLL were cultured with purified B cells or T4 and B cells from normal donors for 7 days with pokeweed mitogen (PWM). IgM, IgA, and IgG produced were determined in the supernatants of these cultures by a heavy chain- specific enzyme-linked immunosorbent assay (ELISA) and compared to those obtained by the corresponding mixtures of T4, T8, and B cells from normal donors. Purified T4 cells from 14 of 20 patients with CLL exhibited defective helper function (P less than .001) to immunoglobulin (Ig) production by purified B cells from normal donors. Purified T4 cells from 6 of these 14 patients were able to suppress significantly (P less than .001) and in a concentration-dependent manner Ig production by mixtures of T4 and B cells from normal donors, in the absence of T8 cells. These suppressor effector T4 cells from certain patients were partially radiosensitive. Purified T8 cells from 8 of 20 patients with CLL exhibited excessive suppressor activity. These cells significantly suppressed (P less than .001), Ig production by mixtures of T4 and B cells from normal donors to a degree significantly higher (P less than .005) than that observed by equal numbers of T8 cells from normal donors. This inhibition was dependent on the numbers of the T8 CLL cells added to the cultures. Excessive suppressor activity by T8 CLL cells was at least in part radiosensitive in four of eight patients. These results demonstrate a wide range of immunoregulatory T-cell abnormalities in patients with CLL. Naturally occurring T4 suppressor effector cells, directly inhibiting Ig production by mixtures of T4 and B cells, in the absence of T8 cells, are present in certain patients with CLL.

scholarly journals Defective helper function of purified T4 cells and excessive suppressor activity of purified T8 cells in patients with B-cell chronic lymphocytic leukemia. T4 suppressor effector cells are present in certain patients

Blood ◽  
1988 ◽  
Vol 71 (6) ◽  
pp. 1551-1560 ◽  
Author(s):  
JE Kunicka ◽  
CD Platsoucas
Keyword(s):  
T Cell ◽  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Lymphocytic Leukemia ◽  
Pokeweed Mitogen ◽  
Suppressor Activity ◽  
Effector Cells ◽  
Helper Function ◽  
Cell Chronic Lymphocytic Leukemia

Abstract We investigated helper and suppressor functions to B-cell responses and T-T cell interactions of purified T4 and T8 cells from 20 untreated patients with B-cell chronic lymphocytic leukemia (CLL). Appropriate mixtures of purified T4 or T8 cells from patients with CLL were cultured with purified B cells or T4 and B cells from normal donors for 7 days with pokeweed mitogen (PWM). IgM, IgA, and IgG produced were determined in the supernatants of these cultures by a heavy chain- specific enzyme-linked immunosorbent assay (ELISA) and compared to those obtained by the corresponding mixtures of T4, T8, and B cells from normal donors. Purified T4 cells from 14 of 20 patients with CLL exhibited defective helper function (P less than .001) to immunoglobulin (Ig) production by purified B cells from normal donors. Purified T4 cells from 6 of these 14 patients were able to suppress significantly (P less than .001) and in a concentration-dependent manner Ig production by mixtures of T4 and B cells from normal donors, in the absence of T8 cells. These suppressor effector T4 cells from certain patients were partially radiosensitive. Purified T8 cells from 8 of 20 patients with CLL exhibited excessive suppressor activity. These cells significantly suppressed (P less than .001), Ig production by mixtures of T4 and B cells from normal donors to a degree significantly higher (P less than .005) than that observed by equal numbers of T8 cells from normal donors. This inhibition was dependent on the numbers of the T8 CLL cells added to the cultures. Excessive suppressor activity by T8 CLL cells was at least in part radiosensitive in four of eight patients. These results demonstrate a wide range of immunoregulatory T-cell abnormalities in patients with CLL. Naturally occurring T4 suppressor effector cells, directly inhibiting Ig production by mixtures of T4 and B cells, in the absence of T8 cells, are present in certain patients with CLL.

scholarly journals T cells in B-cell chronic lymphocytic leukemia: quantitative assessment of cytotoxic and interleukin-2-producing lymphocyte precursors by limiting dilution analysis

Blood ◽  
1989 ◽  
Vol 73 (6) ◽  
pp. 1622-1626
Author(s):  
O Janssen ◽  
C Nerl ◽  
D Kabelitz
Keyword(s):  
T Cells ◽  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Cytotoxic T Cells ◽  
Interleukin 2 ◽  
Lymphocytic Leukemia ◽  
Limiting Dilution ◽  
Cell Chronic Lymphocytic Leukemia

Controversy exists as to the functional capacity of T lymphocytes in patients with B-cell chronic lymphocytic leukemia (CLL). We have used a limiting dilution (LD) culture approach to quantitatively assess frequencies of proliferating lymphocyte precursors (PLP), cytotoxic lymphocyte precursors (CLP), and interleukin-2 (IL-2)-producing helper lymphocyte precursors (HLP). Unseparated mononuclear cells (MNC) or purified T cells (E+) and leukemic B cells (E-) were cocultured under LD conditions with irradiated OKT3 hybridoma cells in the absence (determination of HLP) or presence of recombinant IL-2 (determination of PLP and CLP). Under these conditions, low frequencies of PLP, HLP, and CLP (f = 1/65 to 1/4600) were measured in unseparated MNC of CLL patients. In contrast, purified T cells (50% to 92% CD3+) contained precursors of proliferating, IL-2-producing and cytotoxic T cells in similar frequency as did T cells from healthy control donors (f = 1/4 to 1/24). Leukemic B cells rigorously depleted of T cells did not give rise to measurable frequencies of PLP, HLP, or CLP (f less than 1/50.000) except in one CLL patient where a significant frequency (f = 1/1700) of HLP was consistently present in E- cells, despite the absence of growth-inducible PLP and CLP. Taken together, these results indicate that comparable numbers of IL-2-producing helper T cells and cytotoxic T cells are present in B-CLL patients and healthy controls, respectively. The data are discussed with respect to reported T cell abnormalities in B-CLL.

scholarly journals Defective T cell-mediated, isotype-specific immunoglobulin regulation in B cell chronic lymphocytic leukemia

Blood ◽  
1988 ◽  
Vol 71 (4) ◽  
pp. 1012-1020 ◽  
Author(s):  
JS Moore ◽  
MB Prystowsky ◽  
RG Hoover ◽  
EC Besa ◽  
PC Nowell
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Cell Activity ◽  
Lymphocytic Leukemia ◽  
Specific Immunoglobulin ◽  
Cell Chronic Lymphocytic Leukemia

Abstract The consistent occurrence of T cell abnormalities in patients with B cell chronic lymphocytic leukemia (B-CLL) suggest that the non- neoplastic host T cells may be involved in the pathogenesis of this B cell neoplasm. Because potential defects of immunoglobulin regulation are evident in B-CLL patients, we investigated one aspect of this by studying the T cell-mediated immunoglobulin isotype-specific immunoregulatory circuit in B-CLL. The existence of class-specific immunoglobulin regulatory mechanisms mediated by Fc receptor-bearing T cells (FcR + T) through soluble immunoglobulin binding factors (IgBFs) has been well established in many experimental systems. IgBFs can both suppress and enhance B cell activity in an isotype-specific manner. We investigated the apparently abnormal IgA regulation in a B-CLL patient (CLL249) whose B cells secrete primarily IgA in vitro. Enumeration of FcR + T cells showed a disproportionate increase in IgA FcR + T cells in the peripheral blood of this patient. Our studies showed that the neoplastic B cells were not intrinsically unresponsive to the suppressing component of IgABF produced from normal T cells, but rather the IgABF produced by the CLL249 host T cells was defective. CLL249 IgABF was unable to suppress IgA secretion by host or normal B cells and enhanced the in vitro proliferation of the host B cells. Size fractionation of both normal and CLL249 IgABF by gel-filtration high- performance liquid chromatography (HPLC) demonstrated differences in the ultraviolet-absorbing components of IgABF obtained from normal T cells v that from our patient with defective IgA regulation. Such T cell dysfunction may not be restricted to IgA regulation, since we have found similar expansion of isotype-specific FcR + T cells associated with expansion of the corresponding B cell clone in other patients with B-CLL. These data suggest that this T cell-mediated regulatory circuit could be significantly involved in the pathogenesis of B-CLL.

scholarly journals Normal cellular counterparts of B cell chronic lymphocytic leukemia

Blood ◽  
1987 ◽  
Vol 70 (2) ◽  
pp. 418-427
Author(s):  
AS Freedman ◽  
AW Boyd ◽  
FR Bieber ◽  
J Daley ◽  
K Rosen ◽  
...  
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Cell Activation ◽  
Interleukin 2 ◽  
Lymphocytic Leukemia ◽  
B Cell Activation ◽  
Activation Antigens ◽  
Cell Chronic Lymphocytic Leukemia

In an attempt to compare B cell chronic lymphocytic leukemia (B-CLL) with its normal cellular counterpart, the cell surface phenotype of 100 cases of B-CLL was determined by using a panel of monoclonal antibodies (MoAbs) directed against B cell-restricted and -associated antigens. The majority of B-CLL cells expressed Ia, B4 (CD19), B1 (CD20), B2 (CD21), surface immunoglobulin (sIg), and T1 (CD5) but lacked C3b (CD35) receptors. In contrast, the overwhelming majority of small unstimulated B cells expressed Ia, B4, B1, B2, sIg, and C3b receptors but lacked detectable T1. Small numbers of weakly sIg+ cells could be identified in peripheral blood and tonsil that coexpressed the B1 and T1 antigens. Approximately 16% of fetal splenocytes coexpressed B1, T1, weak sIg, B2, and Ia but lacked C3b receptors and therefore closely resembled most B-CLL cells. With the phenotypic differences between the majority of small unstimulated B cells and B-CLL cells, we examined normal in vitro activated B cells and B-CLL cells for the expression of B cell-restricted and -associated activation antigens. Of 20 cases examined, virtually all expressed B5, and approximately 50% of the cases expressed interleukin-2 receptors (IL-2R) and Blast-1. Normal B cells were activated with either anti-Ig or 12–0-tetradecanoylphorbol- beta-acetate (TPA) and then were examined for coexpression of B1, T1, and the B cell activation antigens B5 and IL-2R. Only cells activated with TPA coexpressed B1 and T1 as well as B5 and IL-2R. B cells activated with either anti-Ig or TPA proliferated in the presence of IL- 2, whereas B-CLL cells did not, although they all expressed the identical 60-kilodalton proteins by immunoprecipitation. These studies are consistent with the notion that B-CLL resembles several minor subpopulations of normal B cells including a population of B cells that are activated in vitro directly through the protein kinase C pathway.

scholarly journals Hypoplastic anemia in B cell chronic lymphocytic leukemia: evolution of T cell-mediated suppression of erythropoiesis in early-stage and late- stage disease

Blood ◽  
1985 ◽  
Vol 66 (3) ◽  
pp. 533-541
Author(s):  
KF Mangan ◽  
L D'Alessandro
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Progenitor Cell ◽  
Lymphocytic Leukemia ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cell ◽  
Cell Chronic Lymphocytic Leukemia

To define further the role of marrow T suppressor lymphocytes in the pathogenesis of the hypoproliferative anemia in all Rai clinical stages of B cell chronic lymphocytic leukemia (CLL), marrow erythroid progenitor cell (CFU-E and BFU-E) frequency, marrow T gamma lymphocyte frequency per 1,000 nucleated marrow cells, and T cell-erythroid progenitor cell interactions were examined in 30 CLL patients and normal control subjects. As compared with control subjects, decreased numbers of CFU-E and BFU-E were found in patient marrow depleted of neoplastic B cells in all Rai stages of the disease. As a group, Rai stage III through IV patients with or without aplasia (CLL-aplasia) had significantly fewer CFU-E and BFU-E than did Rai O through II stage patients. The numbers of T gamma cells infiltrating CLL marrows were increased 3, 9, and 20 times normal in Rai O through II, Rai III through IV, and CLL-aplasia groups, respectively. Removal of T cells from marrow increased growth of CFU-E and BFU-E in all Rai O through IV patients, but the increase was significant in the CLL-aplasia group only (P less than .05). However, autologous coculture of marrow T cells or T gamma cells but not B cells with marrow B + T-depleted null cells at ratios of 0.2:1 to 1:1 suppressed CFU-E and BFU-E growth in all three patient groups. We conclude that the hypoproliferative anemia occurring in the course of B cell CLL is due to gradual accumulation in the marrow of T gamma lymphocytes which suppress erythroid progenitor cell growth. T gamma cell suppression of erythropoiesis and marrow T gamma cell expansion is detectable in the earliest Rai stages of the disease.

scholarly journals Hypoplastic anemia in B cell chronic lymphocytic leukemia: evolution of T cell-mediated suppression of erythropoiesis in early-stage and late- stage disease

Blood ◽  
1985 ◽  
Vol 66 (3) ◽  
pp. 533-541 ◽  
Author(s):  
KF Mangan ◽  
L D'Alessandro
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Progenitor Cell ◽  
Lymphocytic Leukemia ◽  
Erythroid Progenitor ◽  
Erythroid Progenitor Cell ◽  
Cell Chronic Lymphocytic Leukemia

Abstract To define further the role of marrow T suppressor lymphocytes in the pathogenesis of the hypoproliferative anemia in all Rai clinical stages of B cell chronic lymphocytic leukemia (CLL), marrow erythroid progenitor cell (CFU-E and BFU-E) frequency, marrow T gamma lymphocyte frequency per 1,000 nucleated marrow cells, and T cell-erythroid progenitor cell interactions were examined in 30 CLL patients and normal control subjects. As compared with control subjects, decreased numbers of CFU-E and BFU-E were found in patient marrow depleted of neoplastic B cells in all Rai stages of the disease. As a group, Rai stage III through IV patients with or without aplasia (CLL-aplasia) had significantly fewer CFU-E and BFU-E than did Rai O through II stage patients. The numbers of T gamma cells infiltrating CLL marrows were increased 3, 9, and 20 times normal in Rai O through II, Rai III through IV, and CLL-aplasia groups, respectively. Removal of T cells from marrow increased growth of CFU-E and BFU-E in all Rai O through IV patients, but the increase was significant in the CLL-aplasia group only (P less than .05). However, autologous coculture of marrow T cells or T gamma cells but not B cells with marrow B + T-depleted null cells at ratios of 0.2:1 to 1:1 suppressed CFU-E and BFU-E growth in all three patient groups. We conclude that the hypoproliferative anemia occurring in the course of B cell CLL is due to gradual accumulation in the marrow of T gamma lymphocytes which suppress erythroid progenitor cell growth. T gamma cell suppression of erythropoiesis and marrow T gamma cell expansion is detectable in the earliest Rai stages of the disease.

scholarly journals Normal cellular counterparts of B cell chronic lymphocytic leukemia

Blood ◽  
1987 ◽  
Vol 70 (2) ◽  
pp. 418-427 ◽  
Author(s):  
AS Freedman ◽  
AW Boyd ◽  
FR Bieber ◽  
J Daley ◽  
K Rosen ◽  
...  
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Cell Activation ◽  
Interleukin 2 ◽  
Lymphocytic Leukemia ◽  
B Cell Activation ◽  
Activation Antigens ◽  
Cell Chronic Lymphocytic Leukemia

Abstract In an attempt to compare B cell chronic lymphocytic leukemia (B-CLL) with its normal cellular counterpart, the cell surface phenotype of 100 cases of B-CLL was determined by using a panel of monoclonal antibodies (MoAbs) directed against B cell-restricted and -associated antigens. The majority of B-CLL cells expressed Ia, B4 (CD19), B1 (CD20), B2 (CD21), surface immunoglobulin (sIg), and T1 (CD5) but lacked C3b (CD35) receptors. In contrast, the overwhelming majority of small unstimulated B cells expressed Ia, B4, B1, B2, sIg, and C3b receptors but lacked detectable T1. Small numbers of weakly sIg+ cells could be identified in peripheral blood and tonsil that coexpressed the B1 and T1 antigens. Approximately 16% of fetal splenocytes coexpressed B1, T1, weak sIg, B2, and Ia but lacked C3b receptors and therefore closely resembled most B-CLL cells. With the phenotypic differences between the majority of small unstimulated B cells and B-CLL cells, we examined normal in vitro activated B cells and B-CLL cells for the expression of B cell-restricted and -associated activation antigens. Of 20 cases examined, virtually all expressed B5, and approximately 50% of the cases expressed interleukin-2 receptors (IL-2R) and Blast-1. Normal B cells were activated with either anti-Ig or 12–0-tetradecanoylphorbol- beta-acetate (TPA) and then were examined for coexpression of B1, T1, and the B cell activation antigens B5 and IL-2R. Only cells activated with TPA coexpressed B1 and T1 as well as B5 and IL-2R. B cells activated with either anti-Ig or TPA proliferated in the presence of IL- 2, whereas B-CLL cells did not, although they all expressed the identical 60-kilodalton proteins by immunoprecipitation. These studies are consistent with the notion that B-CLL resembles several minor subpopulations of normal B cells including a population of B cells that are activated in vitro directly through the protein kinase C pathway.

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