Positive Regulation of Lyn Kinase by CD148 Is Required for B Cell Receptor Signaling in B1 but Not B2 B Cells

Publication date: Available online 23 November 2016
Source:Immunity
Author(s): Katarzyna M. Skrzypczynska, Jing W. Zhu, Arthur Weiss
B1 and B2 B cells differ in their ability to respond to T-cell-independent (TI) antigens. Here we report that the Src-family kinase (SFK) regulator CD148 has a unique and critical role in the initiation of B1 but not B2 cell antigen receptor signaling. CD148 loss-of-function mice were found to have defective B1 B-cell-mediated antibody responses against the T-cell-independent antigens NP-ficoll and Pneumovax 23 and had impaired selection of the B1 B cell receptor (BCR) repertoire. These deficiencies were associated with a decreased ability of B1 B cells to induce BCR signaling downstream of the SFK Lyn. Notably, Lyn appeared to be selectively regulated by CD148 and loss of this SFK resulted in opposite signaling phenotypes in B1 and B2 B cells. These findings reveal that the function and regulation of Lyn during B1 cell BCR signaling is distinct from other B cell subsets.

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Teaser

In conventional B cell BCR signaling, CD45 and CD148 are redundant positive regulators of SFKs. Skrzypczynska and colleagues demonstrate a unique requirement for CD148 in B1 B cells due to its selective activation of the SFK Lyn, which appears to have a critical positive regulatory role in B1 BCR signaling.


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