Impaired expression of cell surface receptors for B cell growth factor by chronic lymphocytic leukemia B cells.
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.
D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002462:Cell Membrane / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D015847:Interleukin-4; D007945:Leukemia, Lymphoid / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000378:metabolism* / Q000502:physiology; D009439:Neuraminidase / Q000494:pharmacology; D011947:Receptors, Antigen, B-Cell / Q000032:analysis* / Q000187:drug effects
D006133:Growth Substances; D008222:Lymphokines; D011947:Receptors, Antigen, B-Cell; D015847:Interleukin-4; D009439:Neuraminidase