Rabbit B cells develop in the bone marrow and migrate to the gut-associated lymphoid tissues (GALT) where they proliferate, form organized follicles, and undergo Ig gene diversification, to develop the primary antibody repertoire. Our goal is to determine the mechanism by which these processes are induced in GALT. I hypothesize that B cells are polyclonally stimulated in GALT in a T-independent manner and/or are stimulated through the B cell activating factor (BAFF) receptors and complement receptors, CD21/CD35.

To test if T cells are required for B cell stimulation in the GALT, I inhibit T cell activation and T-B cell interactions in vivo, by injecting newborn rabbits with recombinant adenoviruses expressing soluble receptors, CTLA4Ig and CD40Ig. I then examine the GALT for development by immunohistochemistry. I am also developing T cell deficient rabbits through a combination of neonatal thymectomy and anti-CD4 mAb treatment. Using a similar approach, I will test if BAFF is required for B cell stimulation, by interfering with the BAFF signaling pathway using a soluble BAFF receptor in vivo. Additionally, B cells can be stimulated through the interactions of complement receptors, CD21 on B cells and CD35 on follicular dendritic cells (FDCs), in an antigen and T-independent manner. To test this possibility, I will introduce a soluble CD21 receptor in vivo, to block the FDC derived co-signal.