B-CELL B-CELL INTERACTION THROUGH INTERCELLULAR-ADHESION MOLECULE-1 AND LYMPHOCYTE FUNCTIONAL ANTIGEN-1 REGULATES IMMUNOGLOBULIN-E SYNTHESIS BY B-CELLS STIMULATED WITH INTERLEUKIN-4 AND ANTI-CD40 ANTIBODY

IgE synthesis by purified human B cells is induced by two signals: a c lass switching factor. most commonly interleukin (IL)-4, and the engag ement of CD40. which is activated through its interaction with CD40 li gand (CD40L) expressed on activated T cells. Thus, the combination of IL-4 and anti-CD40 monoclonal antibody (mAb) has been shown to stimula te IgE production in vitro by highly purified B cells. In this T cell- independent system, strong homotypic aggregation of B cells is observe d prior to the production of IgE. Flow cytometric analysis and cell bi nding assays showed that the stimulation of purified B cells with anti -CD40 mAb plus IL-4 resulted in a striking increase of intercellular a dhesion molecule (ICAM) 1(CD54) expression, an induction of CD43 and a n avidity change of lymphocyte functional antigen (LFA)-1(CD11a/CD18), with little augmentation of CD18 expression. Addition of anti-ICAM-1 mAb caused an inhibition of homotypic aggregation but augmented IgE sy nthesis by B cells stimulated with anti-CD40 mAb and IL-4, although it did not affect B cell proliferation, or IL-6 production by the B cell s. Among the mAb against counter-receptors for ICAM-1 tested. anti-CD1 1a mAb suppressed IgE synthesis, while anti-CD18 mAb and anti-CD43 mAb had little effect. The enhancing or inhibitory effect of anti-ICAM-1 mAb or anti-CD11a mAb on IgE production was achieved by the increased or decreased expression of germline C epsilon transcripts by B cells s timulated with anti-CD40 mAb and IL-3. These results indicate that B c ell-B cell interaction through ICAM 1 and one of its counter receptors , LFA-1, regulates IgE synthesis by modulating C epsilon germ-line tra nscription.