Two distinct subpopulations of marginal zone B cells exhibit differential antibody-producing capacities and radioresistance

Marginal zone (MZ) B cells, which are splenic innate-like B cells that rapidly secrete antibodies (Abs) against blood-borne pathogens, are composed of heterogeneous subpopulations. Here, we showed that MZ B cells can be divided into two distinct subpopulations according to their CD80 expression levels. CD80^high MZ B cells exhibited greater Ab-producing, proliferative, and IL-10-secreting capacities than did CD80^low MZ B cells. Notably, CD80^high MZ B cells survived 2-Gy whole-body irradiation, whereas CD80^low MZ B cells were depleted by irradiation and then repleted with one month after irradiation. Depletion of CD80^low MZ B cells led to accelerated development of type II collagen (CII)-induced arthritis upon immunization with bovine CII. CD80^high MZ B cells exhibited higher expression of genes involved in proliferation, plasma cell differentiation, and the antioxidant response. CD80^high MZ B cells expressed more autoreactive B cell receptors (BCRs) that recognized double-stranded DNA or CII, expressed more immunoglobulin heavy chain sequences with shorter complementarity-determining region 3 sequences, and included more clonotypes with no N-nucleotides or with B-1a BCR sequences than CD80^low MZ B cells. Adoptive transfer experiments showed that CD21⁺CD23⁺ transitional 2 MZ precursors preferentially generated CD80^low MZ B cells and that a proportion of CD80^low MZ B cells were converted into CD80^high MZ B cells; in contrast, CD80^high MZ B cells stably remained CD80^high MZ B cells. In summary, MZ B cells can be divided into two subpopulations according to their CD80 expression levels, Ab-producing capacity, radioresistance, and autoreactivity, and these findings may suggest a hierarchical composition of MZ B cells with differential stability and BCR specificity.