Expansion of B2 cells in the peritoneal cavity of PD-1−/− mice

Abstract

Abstract The programmed death-1 receptor/ligand pair (PD-1/PD-L1) functions to temper T cell activation. Mice lacking PD-1 have a normal lifespan while exhibiting T cell expansion in their lymphoid tissue. We explored this mutant further focusing on B cell biology. By flow cytometry, C57Bl/6J PD-1−/− spleen (SP) B cells were similar to those of wildtype (WT) mice. However, their peritoneal cavity (PerC) B cells had more IgMloIgDhi B cells (B2 subset) and fewer CD11bloCD19+ and CD5loCD19+ B cells (B1b/B1a subsets). Consistent with their B cell expansion, serum IgM, IgG3, IgG1, and IgA levels were 1.5–2.5 fold greater in PD-1−/− mice. Likewise, responses to thymus-dependent (FITC-OVA) and thymus-independent type-1 and −2 antigens (FITC-LPS, FITC-DEX) were greater than those of WT mice. As expected from prior studies, more activated or effector/memory (CD25+CD62L−CD44+) CD4+ T cells were found in the PD-1−/− SP. However this was not the case in the PerC where CD8+CD62L−CD44+ T cells were increased relative to WT. The latter likely contributed to the 3-fold greater level of IFNg production found for PD-1−/− PerC cells. PerC B2 cell expansion was less evident in older mice, perhaps reflecting sequelae of thymic involution with aging. These observations will be discussed in the context of T cell modulation impacting B cell biology. Supported by NIH AREA program (R15 AI 060356-01, R15 CA 136901). Supported by NIH AREA program grants R15 AI 060356-01 and R15 CA 136901.