Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 111, Issue 32, Pages 11786-11791Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1323557111
Keywords
B lymphocyte; acquired immunity; germinal center; antigen-presenting cell; zinc signaling
Categories
Funding
- KAKENHI Grants [25860371, 23592239]
- RIKEN Junior Research Associate Program
- Mishima Kaiun Memorial Foundation
- Grants-in-Aid for Scientific Research [24689042, 23592239, 26462324, 24390098, 26670472, 25118732, 26293229, 25462875, 25860371] Funding Source: KAKEN
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The humoral immune response, also called the antibody-mediated immune response, is one of the main adaptive immune systems. The essential micronutrient zinc (Zn) is known to modulate adaptive immune responses, and dysregulated Zn homeostasis leads to immunodeficiency. However, the molecular mechanisms underlying this Zn-mediated modulation are largely unknown. Here, we show that the Zn transporter SLC39A10/ZIP10 plays an important role in B-cell antigen receptor (BCR) signal transduction. Zip10-deficiency in mature B cells attenuated both T-cell-dependent and -independent immune responses in vivo. The Zip10-deficient mature B cells proliferated poorly in response to BCR cross-linking, as a result of dysregulated BCR signaling. The perturbed signaling was found to be triggered by a reduction in CD45R phosphatase activity and consequent hyperactivation of LYN, an essential protein kinase in BCR signaling. Our data suggest that ZIP10 functions as a positive regulator of CD45R to modulate the BCR signal strength, thereby setting a threshold for BCR signaling in humoral immune responses.
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