CD11c-Expressing B Cells Are Located at the T Cell/B Cell Border in Spleen and Are Potent APCs

Abstract

Besides secretion of antigen-specific antibodies, B cells may play an important role in the generation of immune responses by efficiently presenting antigen to T cells. We and others recently described a subpopulation of CD11c+ B cells (Age/autoimmune associated B cells, ABCs) which appear with age, during virus infections and at the onset of some autoimmune diseases and which participate in autoimmune responses by secreting autoantibodies. Here we assessed the ability of these cells to present antigen and activate antigen-specific T cells. We demonstrated that ABCs present antigen to T cells, in vitro and in vivo, better than follicular B cells (FO cells) do. Our data indicate that ABCs express higher levels of the chemokine receptor, CCR7, and have higher responsiveness to CCL21 and CCL19 than FO cells and are localized at T/B cell border in spleen. Using multiphoton microscopy we show that, in vivo, CD11c+ B cells form significantly more stable interactions with T cells than Follicular B cells do. Together these data identify a previously undescribed role for ABCs as potent antigen-presenting cells and suggest another potential mechanism by which these cells can influence immune responses and/or the development of autoimmunity.

Age-Associated B Cells: A T-bet–Dependent Effector with Roles in Protective and Pathogenic Immunity

“…For example, early studies showed that ABCs obtained from aged animals can present antigen and tend to induce Th17 polarization (22). More recent findings extend these ideas and also suggest that ABCs obtained from aged or autoimmune mice process and present antigen more efficiently that other B cells (33). …”

Ageing adversely affects the migration and function of marginal zone B cells

“…2c). These age/autoimmune‐associated B cells have been characterized elsewhere and will not be a primary focus of this study 17, 18, 19, 20. These data show that ageing is associated with significant dynamic changes to the frequency and number of certain B‐cell populations in the spleen.…”

Fc Receptor–like 5 Expression Distinguishes Two Distinct Subsets of Human Circulating Tissue–like Memory B Cells

“…/CD11c + B cell subset, called age-associated B cells, which has increased capacity to respond to TLR stimulation, present Ag, and secrete autoantibodies, accumulates in aged mice and also appears in mice with certain viral infections and autoimmune conditions (41)(42)(43). Several features of murine age-associated B cells are shared with human FCRL5 + TLM B cells, including reduced response to BCR and CD40 stimulation, accumulation in chronic viral infections and autoimmune conditions, and elevated expression of CD11c, MHC class II, CD80, CD86, CD95, and T-bet (42,44).…”

“…Several features of murine age-associated B cells are shared with human FCRL5 + TLM B cells, including reduced response to BCR and CD40 stimulation, accumulation in chronic viral infections and autoimmune conditions, and elevated expression of CD11c, MHC class II, CD80, CD86, CD95, and T-bet (42,44). Nevertheless, this mouse subset harbors distinct attributes, including robust differentiation into Ab-secreting cells in response to combined TLR and BCR stimulation (41), elevated CCR7 expression that was proposed to lead to localization of the cells at the splenic T/B border (43), and uncompromised survival in culture independent of BAFF (41). It is not known whether TLM B cells accumulate with aging in humans.…”