期刊
NATURE IMMUNOLOGY
卷 11, 期 6, 页码 535-U107出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.1877
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资金
- National Institutes of Health [AI43603, AI40614, K08AI78533]
- National Health and Medical Research Council
- Arthritis Australia
Memory B and plasma cells (PCs) are generated in the germinal center (GC). Because follicular helper T cells (T-FH cells) have high expression of the immunoinhibitory receptor PD-1, we investigated the role of PD-1 signaling in the humoral response. We found that the PD-1 ligands PD-L1 and PD-L2 were upregulated on GC B cells. Mice deficient in PD-L2 (Pdcd1lg2(-/-)), PD-L1 and PD-L2 (Cd274(-/-)Pdcd1lg2(-/-)) or PD-1 (Pdcd1(-/-)) had fewer long-lived PCs. The mechanism involved more GC cell death and less T-FH cell cytokine production in the absence of PD-1; the effect was selective, as remaining PCs had greater affinity for antigen. PD-1 expression on T cells and PD-L2 expression on B cells controlled T-FH cell and PC numbers. Thus, PD-1 regulates selection and survival in the GC, affecting the quantity and quality of long-lived PCs.
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