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- Title
Peripheral apoptosis and limited clonal deletion during physiologic murine B lymphocyte development.
- Authors
Simpson, Mikala JoAnn; Newen, Anna Minh; McNees, Christopher; Sharma, Sukriti; Pfannenstiel, Dylan; Moyer, Thomas; Stephany, David; Douagi, Iyadh; Wang, Qiao; Mayer, Christian Thomas
- 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. Self-tolerance is established during B cell development but the contribution of clonal deletion, receptor editing, anergy and apoptosis is debated. Here we show that although apoptosis does occur in a high proportion of transitional B cells after exiting the bone marrow, the reactivity of apoptotic B cells does not differ from that of viable cells, which argues against apoptosis as major mechanism to eliminate self-reactive and polyreactive clones.
- Subjects
B cells; BONE marrow cells; APOPTOSIS; B cell receptors; BONE marrow
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-49062-x