HUMAN B CELL DIFFERENTIATION: DEPENDENCE ON INTERACTIONS WITH MONOCYTES AND T LYMPHOCYTES VIA CD40, CD80 (B7.1), AND THE CD2-LIGANDS CD48 AND CD58 (LFA-3)

B cell differentiation depends on cellular interactions with T lymphocytes and monocytes via adhesion molecules (AM). In order to characterize AM which are required for B cell differentiation immunoglobulin production using unseparated peripheral blood mononuclear cells (PBMC) was studied. Unstimulated human PBMC were cultured for 9 days with mAb directed at CD2/CD48, /CD58, CD59, CD5/CD72, CD11a—CD18/CD54, CD28/CD80, CD86, CD40/CD40L, or rat CD2 (control). B cell differentiation was quantified measuring IgM and in some cases IgA, IgG, and IgE production. IgM levels were significantly reduced by mAb against CD40, CD48, CD58 and CD80. The reduction was not due to isotype switching to IgA, IgG or IgE. The role of CD40, CD48, CD58 and CD80 was further investigated after depletion of different cell types. Depletion of monocytes and NK cells resulted in no detectable IgM production irrespective of added mAbs. In contrast, IgM production was still present after depletion of T cells and NK cells. Only mAb against CD80 and CD48 significantly reduced IgM production, the reduction of IgM production by anti-CD40 mAb was less than in the presence of T cells. Importantly, anti-CD58 mAb had no effect on IgM production after T cell and NK cell depletion. Taken together, the AM CD40, CD48, CD58, and CD80 are involved in Ig production of unseparated PBMCs. In this model of B cell differentiation only the AM CD58 depend on the presence of T cells while CD48 and CD80 help was found to be T cell independent.