Kang S, Keener AB, Jones SZ, Benschop RJ, Caro-Maldonado A, Rathmell JC, Clarke SH, Matsushima GK, Whitmire JK, Vilen BJ. IgG-Immune Complexes Promote B Cell Memory by Inducing BAFF. Journal of immunology (Baltimore, Md. : 1950). 2016 Jan 1;196(196). 196-206. PMID: 26621863 [PubMed] PMCID: PMC4684997 NIHMSID: NIHMS734986.
Memory B cell responses are vital for protection against infections but must also be regulated to prevent autoimmunity. Cognate T cell help, somatic hypermutation, and affinity maturation within germinal centers (GCs) are required for high-affinity memory B cell formation; however, the signals that commit GC B cells to the memory pool remain unclear. In this study, we identify a role for IgG-immune complexes (ICs), FcγRs, and BAFF during the formation of memory B cells in mice. We found that early secretion of IgG in response to immunization with a T-dependent Ag leads to IC-FcγR interactions that induce dendritic cells to secrete BAFF, which acts at or upstream of Bcl-6 in activated B cells. Loss of CD16, hematopoietic cell-derived BAFF, or blocking IC:FcγR regions in vivo diminished the expression of Bcl-6, the frequency of GC and memory B cells, and secondary Ab responses. BAFF also contributed to the maintenance and/or expansion of the follicular helper T cell population, although it was dispensable for their formation. Thus, early Ab responses contribute to the optimal formation of B cell memory through IgG-ICs and BAFF. Our work defines a new role for FcγRs in GC and memory B cell responses.