Positive selection focuses the VH12 B-cell repertoire towards a single B1 specificity with survival function

Abstract

B cells of varying antigen specificities are consistently present in the unmanipulated repertoire. These B cells appear to belong to the marginal zone (MZ) and B1 B-cell subsets and provide protection to the blood and lymph, respectively. Some are specific for self-antigens, suggesting that they are selected based on specificity for self but have a protective role against foreign pathogens. One of these specificities is for phosphatidylcholine (PtC). Anti-PtC B cells comprise 5-8% of the B1 repertoire and are protective against bacterial pathogens. In general, they are restricted to the expression of two VH/Vkappa combinations, VH11/Vkappa9 and VH12/Vkappa4/5H. This review focuses on the differentiation of VH12 anti-PtC B cells. They undergo a series of positive selection events beginning at the pre-B-cell stage that enriches for those with a VHCDR3 and L chain required for PtC binding and eliminating the majority of VH12 B cells that lack the ability to bind PtC. Thus, positive selection focuses the VH12 repertoire toward PtC, ensuring that anti-PtC VH12 B cells are a significant component of the B1-cell repertoire in all individuals.