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Tracing Self-Reactive B Cells in Normal Mice.

Publication ,  Journal Article
Nojima, T; Reynolds, AE; Kitamura, D; Kelsoe, G; Kuraoka, M
Published in: J Immunol
July 1, 2020

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 apoptosis regulates differently persistent and ephemeral autoreactive B cells. The self-reactivity and longevity of CD93-IgM-/loIgDhi B cells and their capacity to proliferate and differentiate into plasmacytes in response to CD40 activation in vitro lead us to propose that this persistent, self-reactive compartment may be the origin of systemic autoimmunity and a potential target for vaccines to elicit protective Abs cross-reactive with self-antigens.

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Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

July 1, 2020

Volume

205

Issue

1

Start / End Page

90 / 101

Location

United States

Related Subject Headings

  • Spleen
  • Single-Cell Analysis
  • Receptors, Antigen, B-Cell
  • Primary Cell Culture
  • Precursor Cells, B-Lymphoid
  • Models, Animal
  • Mice
  • Lymph Nodes
  • Immunology
  • Half-Life
 

Citation

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Nojima, T., Reynolds, A. E., Kitamura, D., Kelsoe, G., & Kuraoka, M. (2020). Tracing Self-Reactive B Cells in Normal Mice. J Immunol, 205(1), 90–101. https://doi.org/10.4049/jimmunol.1901015
Nojima, Takuya, Alexander E. Reynolds, Daisuke Kitamura, Garnett Kelsoe, and Masayuki Kuraoka. “Tracing Self-Reactive B Cells in Normal Mice.J Immunol 205, no. 1 (July 1, 2020): 90–101. https://doi.org/10.4049/jimmunol.1901015.
Nojima T, Reynolds AE, Kitamura D, Kelsoe G, Kuraoka M. Tracing Self-Reactive B Cells in Normal Mice. J Immunol. 2020 Jul 1;205(1):90–101.
Nojima, Takuya, et al. “Tracing Self-Reactive B Cells in Normal Mice.J Immunol, vol. 205, no. 1, July 2020, pp. 90–101. Pubmed, doi:10.4049/jimmunol.1901015.
Nojima T, Reynolds AE, Kitamura D, Kelsoe G, Kuraoka M. Tracing Self-Reactive B Cells in Normal Mice. J Immunol. 2020 Jul 1;205(1):90–101.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

July 1, 2020

Volume

205

Issue

1

Start / End Page

90 / 101

Location

United States

Related Subject Headings

  • Spleen
  • Single-Cell Analysis
  • Receptors, Antigen, B-Cell
  • Primary Cell Culture
  • Precursor Cells, B-Lymphoid
  • Models, Animal
  • Mice
  • Lymph Nodes
  • Immunology
  • Half-Life