Can Age-Associated B cells (ABC) Contribute to Anti-Viral Immunity?

Abstract

Abstract With age, follicular helper T cell (TFH) dependent B cell responses erode, reducing germinal center formation, follicular B cell antibody responses and memory. Aged mice and humans develop an additional B cell population, termed age-associated B cells (ABC), that lack CD21 and CD23 and may produce TFH independent antibodies. The aged ABC population is heterogeneous, with some expressing transcription factors and adhesion molecules suggesting antigen exposure, and such ABC have been implicated in autoimmunity. Similarly, we found a unique population of responding B cells following influenza A virus (IAV) infection of aged mice that was Fas+/GL7− and we called infection induced-ABC (iABC). We asked if the CD21−CD23− ABC are progenitors of these non-follicular iABC. Upon IAV infection, transferred ABC gave rise to an iABC (Fas+GL7−) population in T and B deficient RAG KO and TFH deficient SAP KO hosts. This ABC-derived iABC population shared the phenotype of iABC in infected aged mice and could become T- cell independent Ab-producing cells. We found that aged ABC can be separated into sIgD+ (putative naïve B cells) and sIgD−(memory-like B cells). When transferred to SAP KO hosts, the sIgD+ ABC efficiently gave rise to iABC, some of which become CD138+ Ab-secreting cells. This suggests that upon T-independent stimulation, the population of sIgD+ABC in aged mice can develop into IAV-specific Ab secreting cells and may thus provide an alternate B cell-mediated pathway of protection against IAV infection. Studies are underway to evaluate the contribution of iABC-produced Ab to IAV protection.