The quantity of CD40 signaling determines the differentiation of B cells into functionally distinct memory cell subsets.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31225793.
- Also identified by DOI 10.7554/eLife.44245 and PMC identifier 6636905.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
In mice, memory B (B<sub>mem</sub>) cells can be divided into two subpopulations: CD80<sup>hi</sup> B<sub>mem</sub> cells, which preferentially differentiate into plasma cells; and CD80<sup>lo</sup> B<sub>mem</sub> cells, which become germinal center (GC) B cells during a recall response. We demonstrate that these distinct responses can be B-cell-intrinsic and essentially independent of B-cell receptor (BCR) isotypes. Furthermore, we find that the development of CD80<sup>hi</sup> B<sub>mem</sub> cells in the primary immune response requires follicular helper T cells, a relatively strong CD40 signal and a high-affinity BCR on B cells, whereas the development of CD80<sup>lo</sup> B<sub>mem</sub> cells does not. Quantitative differences in CD40 stimulation were enough to recapitulate the distinct B cell fate decisions in an in vitro culture system. The quantity of CD40 signaling appears to be translated into NF-κB activation, followed by BATF upregulation that promotes B<sub>mem</sub> cell differentiation from GC B cells.
Medical subject headings
- B-Lymphocytes
- CD40 Antigens
- Immunologic Memory
- Receptors, Antigen, B-Cell