IMPAIRED EXPRESSION OF CELL-SURFACE RECEPTORS FOR B-CELL GROWTH-FACTOR BY CHRONIC LYMPHOCYTIC-LEUKEMIA B-CELLS

  • 1 April 1986
    • journal article
    • research article
    • Vol. 67  (4) , 943-948
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 repsonse 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.