Two Distinct Subpopulations of Marginal Zone B Cells Exhibit Differential Antibody-Producing Capacity and Radioresistance

Abstract

Abstract Marginal zone (MZ) B cells are innate-like B cells that not only rapidly secrete antibodies (Abs) against blood-borne pathogens but also serve Ab-independent functions such as antigen presentation and immune regulation, which may reflect their heterogeneity. Here, we discovered a subpopulation of MZ B cells that expressed higher levels of CD80, but not CD86, in naïve mice. CD80high MZ B cells revealed higher Ab-producing, proliferative, and IL-10-secreting capacities than CD80low MZ B cells. Notably, the CD80high MZ B cells survived 2 Gy whole-body irradiation, whereas CD80low MZ B cells were preferentially depleted by the irradiation and repleted in a month after the irradiation. The CD80high MZ B cells expressed higher levels of genes involved in proliferation, plasma cell differentiation, antioxidant response, and immune regulation. The CD80high MZ B cells contained autoreactive BCRs reactive to double-stranded DNA or type II collagen. Next-generation sequencing revealed more immunoglobulin heavy chains with a shorter complementarity-determining region 3 and no N-nucleotides in the CD80high MZ B cells than in CD80low MZ B cells. In summary, MZ B cells can be divided into two populations differing in CD80 expression, Ab-productive capacity, radioresistance, and B cell receptor repertoire, which may have different homeostatic functions.