Enhanced BCR signaling inflicts early plasmablast and germinal center B cell death

Juan Carlos Yam-Puc, Lingling Zhang, Raul Maqueda Alfaro, Laura Garcia Ibanez, Yang Zhang, Jessica Davies, Yotis Senis, Michael Snaith, Kai Toellner

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Abstract

It is still not clear how B cell receptor (BCR) signaling intensity affects plasma cell (PC) and germinal center (GC) B cell differentiation. We generated Cγ1Cre/wtPtpn6fl/fl mice where SHP-1, a negative regulator of BCR signaling, is deleted rapidly after B cell activation. Although immunization with T-dependent antigens increased BCR signaling, it led to PC reduction and increased apoptosis. Dependent on the antigen, the early GC B cell response was equally reduced and apoptosis increased. At the same time, a higher proportion of GC B cells expressed cMYC, suggesting GC B cell-Tfh cell interactions may be increased. GC B cell numbers returned to normal at later stages, whereas affinity maturation was suppressed in the long term. This confirms that BCR signaling not only directs affinity-dependent B cell selection but also, without adequate further stimulation, can inflict cell death, which may be important for the maintenance of B cell tolerance.
Original languageEnglish
Article number102038
Pages (from-to)102038
JournaliScience
Volume24
Issue number2
Early online date7 Jan 2021
DOIs
Publication statusPublished - 19 Feb 2021

Bibliographical note

Funding Information:
We are grateful to Benjamin G. Neel (NYU School of Medicine) for Ptpn6 fl/wt mice and S. Casola (IFOM, Milan, Italy) for Cγ1 Cre/wt mice. We thank Mark J. Shlomchik and Wei Luo for helpful discussion. In addition, we would like to thank at the Biomedical Service Unit, Flow Cytometry Services, and Microscopy and Imaging Services at the University of Birmingham. This work was supported by grants from the BBSRC BB/M025292/1 to K.-M.T. and post-doctoral fellowship program from National Council of Science and Technology, Mexico (CONACYT-Mexico) to J.C.Y.-P.

Keywords

  • Immunology
  • cell biology
  • immune system

ASJC Scopus subject areas

  • General

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