CD86 (B7-2) ON HUMAN B-CELLS - A FUNCTIONAL-ROLE IN PROLIFERATION ANDSELECTIVE DIFFERENTIATION INTO IGE-PRODUCING AND IGG4-PRODUCING CELLS

Immunoglobulin (Ig) E production by B cells requires two primary signa ls provided by T cells, interleukin (IL)-4 or IL-13 and CD40 ligand (C D40L), In addition, costimulatory signals, such as CD23-CD21 interacti on, contribute further ensuring a selective control over this producti on. Recently, CD28, expressed on T cells, has been reported to be invo lved in this process, The CD28 ligands, CD80 (B7-1) and CD86 (B7-2), a re expressed on human tonsillar B cells, and their expression is up-re gulated by IL-4, IL-13, and/or an anti-CD40 monoclonal antibody (mAb), We have investigated whether signaling via the B7 molecules affects I gE synthesis, Human B cells were stimulated by IL-4 plus anti CD40 mAb in the presence of different anti-B7 mAbs. Cross-linking of CD86 with IT2.2 potentiated IgE and IgG4 production and E transcripts expressio n, The production of the other isotypes was not modulated, Conversely, the anti-CD80 and the other anti-CD86 mAbs tested had no effect, The increase of IgE and IgG4 production induced by IT2.2 was accompanied b y an increase in proliferation, in cell surface density of CD23, and i n CD23 binding to CD21-expressing B cells, In contrast, the expression of other B cell surface molecules such as CD11a, CD30, and CD58 remai ned unaffected, Since IT2.2 favors CD23-CD21 pairing, we tested whethe r blocking this interaction affected IT2.2-increased IgE production, T he neutralizing anti-CD23 mAb, Mab 25, caused a dose-dependent inhibit ion of the effect of IT2.2 on IgE synthesis, Finally, IT2.2 potentiati on on B cell proliferation and IgE production required the two primary signals, IL-4 and anti-CD40 mAb, since IT2.2 alone or in combination with only one of these stimuli did not show any effect on B cells, Thi s study is the first demonstration of a signaling role for CD86, Toget her with IL-4 or IL-13 and CD40L, CD86 favors CD23-CD21 pairing and co nsequently functions as a selective and potent costimulus for human Ig E and IgG4 synthesis.