Fc Receptor-Like 6 (FCRL6) Discloses Progenitor B Cell Heterogeneity That Correlates With Pre-BCR Dependent and Independent Pathways of Natural Antibody Selection.

ABSTRACT: B-1a cells produce "natural" antibodies (Abs) to neutralize pathogens and clear neo self-antigens, but the fundamental selection mechanisms that shape their polyreactive repertoires are poorly understood. Here, we identified a B cell progenitor subset defined by Fc receptor-like 6 (FCRL6) expression, harboring innate-like defense, migration, and differentiation properties conducive for natural Ab generation. Compared to FCRL6^- pro B cells, the repressed mitotic, DNA damage repair, and signaling activity of FCRL6⁺ progenitors, yielded V_H repertoires with biased distal Ighv segment accessibility, constrained diversity, and hydrophobic and charged CDR-H3 sequences. Beyond nascent autoreactivity, V_H11 productivity, which predominates phosphati

SUBMITTER: Honjo K 

PROVIDER: S-EPMC7033751 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature