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.

Homeostasis and regulation of autoreactive B cells

In contrast to the previous belief that autoreactive B cells are eliminated from the normal repertoire of B cells,many autoreactive B cells actually escape clonal deletion and develop into mature B cells.These autoreactive B cells in healthy individuals perform some beneficial functions in the host and are homeostatically regulated by regulatory T and B cells or other mechanisms to prevent autoimmune diseases.Autoreactive B-1 cells constitutively produce polyreactive natural antibodies for tissue homeostasis.Recently,autoreactive follicular B cells were reported to participate actively in the germinal center reaction.Furthermore,the selection and usefulness of autoreactive marginal zone(MZ)B cells found in autoimmune diseases are not well understood,although the repertoire of MZ B-cell receptors(BCRs)is presumed to be biased to detect bacterial antigens.In this review,we discuss the autoreactive B-cell populations among all three major B-cell subsets and their regulation in immune responses and diseases.