Abstract
B-1 cells represent an innate-like early-developing B cell population, whose existence as an independent lymphocyte subset has been questioned in the past. Recent molecular and lineage tracing studies have not only confirmed their unique origins and differentiation paths, they have also provided a rationale for their distinctive functionalities compared to conventional B cells. This review summarizes our current understanding of B-1 cell development, and the activation events that regulate B-1 cell responses to self and foreign antigens. We discuss the unresolved question to what extent BCR engagement, that is, antigen-specificity versus innate signaling contributes to B-1 cell's participation in tissue homeostasis and immune defense as providers of 'natural' and antigen-induced antibody responses, and as cytokine-producing immune regulators.