CD40 SIGNALING IN ILEAL PEYERS PATCH A CELLS - IMPLICATIONS FOR T-CELL-DEPENDENT ANTIGEN SELECTION

The ileal Peyer's patch (PP) plays a central role in a cell developmen t in young sheep and it is hypothesized that this a cell development o ccurs independent of extrinsic antigen and T cells, Therefore, it was of interest to examine ileal PP follicular (iPf) B cell responses to C D40 ligand, a molecule integral to T cell-dependent B cell development , A variable level of CD40 expression was detected on a subpopulation of iPfB cells and J558L cells, expressing a membrane form of mouse CD4 0 ligand (mCD40L), interacted specifically with the CD40 molecule on i PfB cells, In response to mCD40L the non-S phase iPfB cells were rescu ed from apoptotic cell death and there was a marked proliferative resp onse but viable cell number remained relatively constant, The mCD40L a lso induced decreased cytoplasmic cAMP levels, blocked anti-lg-induced iPfB cell death and induced functional IL-2 receptor expression on a subpopulation of iPfB cells, Many of the mCD40L-induced responses of i PfB cells were similar to those reported for germinal centre and immat ure B cells, and indicated that a cognate T cell-a cell interaction co uld influence iPfB cell proliferation and differentiation, Finally, th at mCD40L induced iPfB cell activation and differentiation was evident as increased expression of CD5, the BAQ44A molecule, the CACT65A mole cule and the expansion of surface lgG1(+) B cells, These mCD40L-induce d phenotypic changes were also observed on subpopulations of freshly i solated iPfB cells and jejunal PP follicular B cells, However, few iPf B cells had a phenotype similar to that observed in co-culture with mC D40L and this suggested that T cell-dependent B cell development may p lay a minor role in ileal PP a cell development, The possible signific ance of CD40 signalling is discussed in terms of the selection of iPfB cells during development.