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 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.

Proliferation of B Cells from Chronic Lymphocytic Leukemia Is Selectively Promoted by B Cell Growth Factor

1989 ◽  
Vol 81 (2) ◽  
pp. 91-97 ◽  
Author(s):  
Melchor Alvarez-Mon ◽  
Antonio de la Hera ◽  
Maria Luisa Gaspar ◽  
Alberto Orfao ◽  
Juan Casas ◽  
...  
Keyword(s):  
B Cells ◽  
Growth Factor ◽  
Cell Growth ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Lymphocytic Leukemia ◽  
B Cell Growth Factor

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.

The expression of B cell surface receptors. III. The murine low-affinity IgE Fc receptor is not expressed on Ly 1 or ‘Ly 1-like’ B cells

1991 ◽  
Vol 3 (4) ◽  
pp. 305-315 ◽  
Author(s):  
Thomas J. Waldschmidt ◽  
Frans G. M. Kroese ◽  
Lorraine T. Tygrett ◽  
Daniel H. Conrad ◽  
Richard G. Lynch
Keyword(s):  
B Cells ◽  
Cell Surface ◽  
B Cell ◽  
Fc Receptor ◽  
Cell Surface Receptors ◽  
Surface Receptors

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 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

scholarly journals Vav Family Proteins Couple to Diverse Cell Surface Receptors

2000 ◽  
Vol 20 (17) ◽  
pp. 6364-6373 ◽  
Author(s):  
Sheri L. Moores ◽  
Laura M. Selfors ◽  
Jessica Fredericks ◽  
Timo Breit ◽  
Keiko Fujikawa ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Surface ◽  
Tyrosine Phosphorylation ◽  
Tyrosine Kinases ◽  
Protein Tyrosine Kinase ◽  
Receptor Activation ◽  
Cell Surface Receptors ◽  
Nucleotide Exchange ◽  
Surface Receptors ◽  
Downstream Signaling

ABSTRACT Vav proteins are guanine nucleotide exchange factors for Rho family GTPases which activate pathways leading to actin cytoskeletal rearrangements and transcriptional alterations. Vav proteins contain several protein binding domains which can link cell surface receptors to downstream signaling proteins. Vav1 is expressed exclusively in hematopoietic cells and tyrosine phosphorylated in response to activation of multiple cell surface receptors. However, it is not known whether the recently identified isoforms Vav2 and Vav3, which are broadly expressed, can couple with similar classes of receptors, nor is it known whether all Vav isoforms possess identical functional activities. We expressed Vav1, Vav2, and Vav3 at equivalent levels to directly compare the responses of the Vav proteins to receptor activation. Although each Vav isoform was tyrosine phosphorylated upon activation of representative receptor tyrosine kinases, integrin, and lymphocyte antigen receptors, we found unique aspects of Vav protein coupling in each receptor pathway. Each Vav protein coprecipitated with activated epidermal growth factor and platelet-derived growth factor (PDGF) receptors, and multiple phosphorylated tyrosine residues on the PDGF receptor were able to mediate Vav2 tyrosine phosphorylation. Integrin-induced tyrosine phosphorylation of Vav proteins was not detected in nonhematopoietic cells unless the protein tyrosine kinase Syk was also expressed, suggesting that integrin activation of Vav proteins may be restricted to cell types that express particular tyrosine kinases. In addition, we found that Vav1, but not Vav2 or Vav3, can efficiently cooperate with T-cell receptor signaling to enhance NFAT-dependent transcription, while Vav1 and Vav3, but not Vav2, can enhance NFκB-dependent transcription. Thus, although each Vav isoform can respond to similar cell surface receptors, there are isoform-specific differences in their activation of downstream signaling pathways.

scholarly journals Functional heterogeneity of B-CLL lymphocytes: dissociated responsiveness to growth factors and distinct requirements for a first activation signal

Blood ◽  
1987 ◽  
Vol 70 (4) ◽  
pp. 1105-1110
Author(s):  
S Karray ◽  
H Merle-Beral ◽  
A Vazquez ◽  
JP Gerard ◽  
P Debre ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Growth Factors ◽  
Growth Factor ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
B Lymphocytes ◽  
Lymphocytic Leukemia ◽  
Functional Heterogeneity ◽  
B Cell Growth Factor ◽  
Directed Growth

We studied the effects of B cell directed growth factors on B lymphocytes from 11 patients with chronic lymphocytic leukemia (B-CLL). B-CLL lymphocytes were costimulated with anti-mu antibody (Ab) and with three growth factor preparations: recombinant IL2, B cell growth factor (BCGF) (20 kiloDalton (kD) BCGF) and a high molecular weight BCGF (50 kD BCGF). IL2 was the more active factor (in six of 11 patients). The effect of IL2 was dependent on a costimulation with anti-mu Ab or occurred independently of anti-mu Ab, according to the patients. This pattern of reactivity did not correlate with the presence or absence of the IL2 receptor (IL2-R) molecule on fresh B-CLL lymphocytes. Five patients responded to the 20 kD BCGF. Although four of them were also strong responders to IL2, one strongly responded to the 20 kD BCGF and did not respond to IL2. Only one patient responded to the 50 kD BCGF. When an anti-IL2-R Ab was introduced into the culture, only the responsiveness to IL2 was abolished: thus both 20 kD and 50 kD BCGFs activate B-CLL lymphocytes independently of the IL2-R. These results show that several B cell directed growth factors can act independently to support the proliferation of B-CLL lymphocytes.

Sign in / Sign up

Export Citation Format

Share Document