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

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Abstract
IgE synthesis by purified human B cells is induced by two signals: a class switching factor, most commonly interleukin (IL)‐4, and the engagement of CD40, which is activated through its interaction with CD40 ligand (CD40L) expressed on activated T cells. Thus, the combination of IL‐4 and anti‐CD40 monoclonal antibody (mAb) has been shown to stimulate IgE production in vitro by highly purified B cells. In this T cell‐independent system, strong homotypic aggregation of B cells is observed prior to the production of IgE. Flow cytometric analysis and cell binding assays showed that the stimulation of purified B cells with anti‐CD40 mAb plus IL‐4 resulted in a striking increase of intercellular adhesion molecule (ICAM)‐1(CD54) expression, an induction of CD43 and an avidity change of lymphocyte functional antigen (LFA)‐1(CD11a/CD18), with little augmentation of CD 18 expression. Addition of anti‐ICAM‐1 mAb caused an inhibition of homotypic aggregation but augmented IgE synthesis 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 cells. Among the mAb against counter‐receptors for ICAM‐1 tested, anti‐CD11a 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 Cεe transcripts by B cells stimulated with anti‐CD40 mAb and IL‐4. These results indicate that B cell‐B cell interaction through ICAM‐1 and one of its counter receptors, LFA‐1, regulates IgE synthesis by modulating Cεe germ‐line transcription.