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

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Abstract
Summary: 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/Vκ combinations, VH11/Vκ9 and VH12/Vκ4/5H. 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.