Nature Communications (Jun 2024)

Peripheral apoptosis and limited clonal deletion during physiologic murine B lymphocyte development

  • Mikala JoAnn Simpson,
  • Anna Minh Newen,
  • Christopher McNees,
  • Sukriti Sharma,
  • Dylan Pfannenstiel,
  • Thomas Moyer,
  • David Stephany,
  • Iyadh Douagi,
  • Qiao Wang,
  • Christian Thomas Mayer

DOI
https://doi.org/10.1038/s41467-024-49062-x
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 13

Abstract

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Abstract Self-reactive and polyreactive B cells generated during B cell development are silenced by either apoptosis, clonal deletion, receptor editing or anergy to avoid autoimmunity. The specific contribution of apoptosis to normal B cell development and self-tolerance is incompletely understood. Here, we quantify self-reactivity, polyreactivity and apoptosis during physiologic B lymphocyte development. Self-reactivity and polyreactivity are most abundant in early immature B cells and diminish significantly during maturation within the bone marrow. Minimal apoptosis still occurs at this site, however B cell receptors cloned from apoptotic B cells show comparable self-reactivity to that of viable cells. Apoptosis increases dramatically only following immature B cells leaving the bone marrow sinusoids, but above 90% of cloned apoptotic transitional B cells are not self-reactive/polyreactive. Our data suggests that an apoptosis-independent mechanism, such as receptor editing, removes most self-reactive B cells in the bone marrow. Mechanistically, lack of survival signaling rather than clonal deletion appears to be the underpinning cause of apoptosis in most transitional B cells in the periphery.