Other
12 Authors
- Li X,
- Tong H,
- Gu H,
- Li Y,
- Klein U,
- Hou F,
- Gadzinsky A,
- Gong L,
- Langdon WY,
- Zou YR,
- Calderon V,
- Kitamura D
| First Author | Li X | Year | 2018 |
| Journal | Immunity | Volume | 48 |
| Issue | 3 | Pages | 530-541.e6 |
| PubMed ID | 29562201 | Mgi Jnum | J:272419 |
| Mgi Id | MGI:6284453 | Doi | 10.1016/j.immuni.2018.03.006 |
| Citation | Li X, et al. (2018) Cbl Ubiquitin Ligases Control B Cell Exit from the Germinal-Center Reaction. Immunity 48(3):530-541.e6 |
| abstractText | Selective expansion of high-affinity antigen-specific B cells in germinal centers (GCs) is a key event in antibody affinity maturation. GC B cells with improved affinity can either continue affinity-driven selection or exit the GC to differentiate into plasma cells (PCs) or memory B cells. Here we found that deleting E3 ubiquitin ligases Cbl and Cbl-b (Cbls) in GC B cells resulted in the early exit of high-affinity antigen-specific B cells from the GC reaction and thus impaired clonal expansion. Cbls were highly expressed in GC light zone (LZ) B cells, where they promoted the ubiquitination and degradation of Irf4, a transcription factor facilitating PC fate choice. Strong CD40 and BCR stimulation triggered the Cbl degradation, resulting in increased Irf4 expression and exit from GC affinity selection. Thus, a regulatory cascade that is centered on the Cbl ubiquitin ligases ensures affinity-driven clonal expansion by connecting BCR affinity signals with differentiation programs. |
