| First Author | Li X | Year | 2020 |
| Journal | J Exp Med | Volume | 217 |
| Issue | 9 | PubMed ID | 32584413 |
| Mgi Jnum | J:305085 | Mgi Id | MGI:6514493 |
| Doi | 10.1084/jem.20191537 | Citation | Li X, et al. (2020) Cbl and Cbl-b control the germinal center reaction by facilitating naive B cell antigen processing. J Exp Med 217(9) |
| abstractText | Antigen uptake and presentation by naive and germinal center (GC) B cells are different, with the former expressing even low-affinity 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 low-affinity BCR into GCs to initiate the process of affinity maturation. |
