TLR9 induces germinal center light zone expansion and augments B cell fate decisions (61.8)

Abstract

Abstract Toll-like receptor 9 (TLR9) signaling regulates inflammatory processes in response to unmethylated CpG motifs that are enriched in viral, bacterial and protozoan DNA. While its roles in dendritic cell (DC) maturation, class switch recombination, and polyclonal B cell proliferation have been extensively studied, the importance of TLR9 in T-dependent germinal center (GC) B cell processes is unclear. To address this problem in vivo, we linked a biotinylated form of the model antigen NP-chicken gamma globulin (NP-CGG) with either biotin-CpG or biotin-nonCpG control (Ctrl) oligos using streptavidin and generated CpG- and Ctrl-conjugates, respectively. As early as 7dpi in the footpad of C57BL/6 mice, we observed TLR9-induced affinity maturation and a selective expansion of GC B cells in the light zone (LZ) where B cells receive survival signals from T follicular helper cells (Tfh) and selection for high affinity clones and distinct B cell fates occurs. We then looked for evidence of TLR9-enhanced selection and found increases in the GC to plasma cell transition as well as a robust increase in GC B cell CD38 expression that signifies memory B cell formation. We conclude that TLR9 selectively enhances light zone processes such as B cell fate decisions and enrichment for high affinity clones. The relationship between LZ expansion and fate decision is a future focus of this project.