Tracing Self-Reactive B Cells in Normal Mice.

Tracing Self-Reactive B Cells in Normal Mice. J Immunol. 2020 May 15;: Authors: Nojima T, Reynolds AE, Kitamura D, Kelsoe G, Kuraoka M Abstract BCR transgenic mice dominate studies of B cell tolerance; consequently, tolerance in normal mice expressing diverse sets of autoreactive B cells is poorly characterized. We have used single B cell cultures to trace self-reactivity in BCR repertoires across the first and second tolerance checkpoints and in tolerized B cell compartments of normal mice. This approach reveals affinity "setpoints" that define each checkpoint and a subset of tolerized, autoreactive B cells that is long-lived. In normal mice, the numbers of B cells avidly specific for DNA fall significantly as small pre-B become immature and transitional-1 B cells, revealing the first tolerance checkpoint. By contrast, DNA reactivity does not significantly change when immature and transitional-1 B cells become mature follicular B cells, showing that the second checkpoint does not reduce DNA reactivity. In the spleen, autoreactivity was high in transitional-3 (T3) B cells, CD93+IgM-/loIgDhi anergic B cells, and a CD93- anergic subset. Whereas splenic T3 and CD93+ anergic B cells are short-lived, CD93-IgM-/loIgDhi B cells have half-lives comparable to mature follicular B cells. B cell-specific deletion of proapoptotic genes, Bak and Bax, resulted in increased CD93-IgM-/loIgDhi B cell numbers but not T3 B cell numbers, suggesting that ...
Source: Journal of Immunology - Category: Allergy & Immunology Authors: Tags: J Immunol Source Type: research