Functional interaction between B cell subpopulations defined by CD23 expression.

Abstract

Using the CD23 monoclonal antibody (mAb) MHM6 and sheep anti-mouse Ig bound to magnetic beads we have obtained highly purified populations of MHM6+ and MHM6- tonsil B cells. We have found that the increased expression of MHM6 reactivity seen on B cells after activation results from up-regulation of antigen on cells already weakly positive and not from expression of new antigen on the previously negative population. The strong proliferative responses of MHM6+ cells seen in the presence of anti-IgM (alpha mu) and interleukin 4 (IL4) or the CDw40 mAb G28-5, and with Staphylococcus aureus Cowan I (SAC), and to a lesser extent with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), resemble that seen among unfractionated B cells. In contrast, the MHM6- population cultured alone responds only weakly to alpha mu + G28-5 or SAC and exhibits virtually no response to alpha mu + IL4 or TPA. With all these mitogenic stimuli, tritiated thymidine uptake by the MHM6- population is augmented three- to sixfold by the addition of mitomycin C (MC)-treated MHM6+ cells. Pretreatment of cells with anti-leukocyte functional antigen 1 mAb has little effect on the subsequent proliferation of the MHM6- population but shows cell contact to be critical for the proliferation of MHM6+ cells. Such pretreatment has revealed that the functional interaction observed between MHM6+ and MHM6- cells is dependent on both cell contact and the presence of an MHM6+ cell-derived soluble component. We have found that addition of soluble CD23, purified from Epstein-Barr virus-transformed lymphoblastoid cell line supernatant, increases the proliferative response of MHM6- tonsil B cells to mitogenic stimuli in the presence of inactivated MHM6+ cells but has no effect on proliferation when MHM6+ cells are absent. By way of contrast to normal B lymphocytes, we have examined functional responses of prolymphocytic leukemia (PLL) B cells. Although these cells, when freshly isolated, show comparable levels of CD23 expression to normal B cells, this expression is not increased upon activation. In addition, in contrast to normal B cells, the PLL MHM6- population cultured alone shows a strong proliferative response to various mitogenic stimuli, comparable to that of MHM6+ or unfractionated cells, and this response is not augmented by the addition of MC-treated MHM6+ cells. Thus, a novel functional interaction is described between normal, but not leukemic, B cell populations defined by their expression of CD23.(ABSTRACT TRUNCATED AT 400 WORDS)