TLR7- and TLR9-responsive human B cells share phenotypic and genetic characteristics

The Journal of Immunology : Official Journal of the American Association of Immunologists
Noa Simchoni, Charlotte Cunningham-Rundles

Abstract

B cells activated by nucleic acid-sensing TLR7 and TLR9 proliferate and secrete immune globulins. Memory B cells are presumably more responsive due to higher TLR expression levels, but selectivity and differential outcomes remain largely unknown. In this study, peripheral blood human B cells were stimulated by TLR7 or TLR9 ligands, with or without IFN-α, and compared with activators CD40L plus IL-21, to identify differentially responsive cell populations, defined phenotypically and by BCR characteristics. Whereas all activators induced differentiation and Ab secretion, TLR stimulation expanded IgM(+) memory and plasma cell lineage committed populations, and favored secretion of IgM, unlike CD40L/IL-21, which drove IgM and IgG more evenly. Patterns of proliferation similarly differed, with CD40L/IL-21 inducing proliferation of most memory and naive B cells, in contrast with TLRs that induced robust proliferation in a subset of these cells. On deep sequencing of the IgH locus, TLR-responsive B cells shared patterns of IgHV and IgHJ usage, clustering apart from CD40L/IL-21 and control conditions. TLR activators, but not CD40L/IL-21, similarly promoted increased sharing of CDR3 sequences. TLR-responsive B cells were characterized b...Continue Reading

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