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The BTB-kelch protein KLHL6 is involved in B-lymphocyte antigen receptor signaling and germinal center formation.


ABSTRACT: 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.

SUBMITTER: Kroll J 

PROVIDER: S-EPMC1265761 | biostudies-literature | 2005 Oct

REPOSITORIES: biostudies-literature

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The BTB-kelch protein KLHL6 is involved in B-lymphocyte antigen receptor signaling and germinal center formation.

Kroll Jens J   Shi Xiaozhong X   Caprioli Arianna A   Liu Hong-Hsing HH   Waskow Claudia C   Lin Keng-Mean KM   Miyazaki Toru T   Rodewald Hans-Reimer HR   Sato Thomas N TN  

Molecular and cellular biology 20051001 19


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  ...[more]

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