| First Author | Kroll J | Year | 2005 |
| Journal | Mol Cell Biol | Volume | 25 |
| Issue | 19 | Pages | 8531-40 |
| PubMed ID | 16166635 | Mgi Jnum | J:101363 |
| Mgi Id | MGI:3603885 | Doi | 10.1128/MCB.25.19.8531-8540.2005 |
| Citation | Kroll J, et al. (2005) The BTB-kelch protein KLHL6 is involved in B-lymphocyte antigen receptor signaling and germinal center formation. Mol Cell Biol 25(19):8531-40 |
| abstractText | BTB-kelch proteins can elicit diverse biological functions but very little is known about the physiological role of these proteins in vivo. Kelch-like protein 6 (KLHL6) is a BTB-kelch protein with a lymphoid tissue-restricted expression pattern. In the B-lymphocyte lineage, KLHL6 is expressed throughout ontogeny, and KLHL6 expression is strongly upregulated in germinal center (GC) B cells. To analyze the role of KLHL6 in vivo, we have generated mouse mutants of KLHL6. Development of pro- and pre-B cells was normal but numbers of subsequent stages, transitional 1 and 2, and mature B cells were reduced in KLHL6-deficient mice. The antigen-dependent GC reaction was blunted (smaller GCs, reduced B-cell expansion, and reduced memory antibody response) in the absence of KLHL6. Comparison of mutants with global loss of KLHL6 to mutants lacking KLHL6 specifically in B cells demonstrated a B-cell-intrinsic requirement for KLHL6 expression. Finally, B-cell antigen receptor (BCR) cross-linking was less sensitive in KLHL6-deficient B cells compared to wild-type B cells as measured by proliferation, Ca2+ response, and activation of phospholipase Cgamma2. Our results strongly point to a role for KLHL6 in BCR signal transduction and formation of the full germinal center response. |
