4.7 Article

Repression of the B cell identity factor Pax5 is not required for plasma cell development

Journal

JOURNAL OF EXPERIMENTAL MEDICINE
Volume 217, Issue 11, Pages -

Publisher

ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20200147

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Funding

  1. Boehringer Ingelheim
  2. European Research Council under the European Union [740349-PlasmaCellControl]
  3. Austrian Industrial Research Promotion Agency [FFG-852936]
  4. Austrian Science Fund (FWF) [DK W1212]

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B cell and plasma cell fates are controlled by different transcriptional networks, as exemplified by the mutually exclusive expression and cross-antagonism of the B cell identity factor Pax5 and the plasma cell regulator Blimp1. It has been postulated that repression of Pax5 by Blimp1 is essential for plasma cell development. Here, we challenged this hypothesis by analyzing the Igh(Pax5/+) mouse, which expressed a Pax5 minigene from the immunoglobulin heavy-chain locus. Despite high Pax5 expression, plasma cells efficiently developed in young Igh(Pax5/+) mice at steady state and upon immunization, while their number moderately declined in older mice. Although Pax5 significantly deregulated the plasma cell expression program, key plasma cell regulators were normally expressed in Igh(Pax5/+) plasma cells. While IgM and IgA secretion by Igh(Pax5/+) plasma cells was normal, IgG secretion was modestly decreased. Hence, Pax5 repression is not essential for robust plasma cell development and antibody secretion, although it is required for optimal IgG production and accumulation of long-lived plasma cells.

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