Cbl and Cbl-b control the germinal center reaction by facilitating naive B cell antigen processing

Xin Li, Liying Gong, Alexandre P. Meli, Danielle Karo-Atar, Weili Sun, Yongrui Zou, Irah L. King, Hua Gu

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Antigen uptake and presentation by naive and germinal center (GC) B cells are different, with the former expressing even lowaffinity BCRs efficiently capture and present sufficient antigen to T cells, whereas the latter do so more efficiently after acquiring high-affinity BCRs. We show here that antigen uptake and processing by naive but not GC B cells depend on Cbl and Cbl-b (Cbls), which consequently control naive B and cognate T follicular helper (Tfh) cell interaction and initiation of the GC reaction. Cbls mediate CD79A and CD79B ubiquitination, which is required for BCR-mediated antigen endocytosis and postendocytic sorting to lysosomes, respectively. Blockade of CD79A or CD79B ubiquitination or Cbls ligase activity is sufficient to impede BCR-mediated antigen processing and GC development. Thus, Cbls act at the entry checkpoint of the GC reaction by promoting naive B cell antigen presentation. This regulation may facilitate recruitment of naive B cells with a lowaffinity BCR into GCs to initiate the process of affinity maturation.

Original languageEnglish
Article numbere20191537
JournalJournal of Experimental Medicine
Volume217
Issue number9
DOIs
StatePublished - 7 Sep 2020
Externally publishedYes

ASJC Scopus subject areas

  • Medicine (all)

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