The role of cGAMP via the STING pathway in modulating germinal center responses and CD4 T cell differentiation

Germinal center (GC) responses are essential for establishing protective, long-lasting immunity through the differentiation of GC B cells (B ) and plasma cells (B ), along with the generation of antigen-specific antibodies. Among the various pathways influencing immune responses, the STING (Stimulat...

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Bibliographic Details
Published in:	Frontiers in immunology Vol. 15; p. 1340001
Main Authors:	Yoon, Mijung, Choi, Yurim, Wi, Taeuk, Choi, Youn Soo, Choi, Jinyong
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers Media S.A 2024
Subjects:	Animals B-Lymphocytes - immunology B-Lymphocytes - metabolism CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism Cell Differentiation - immunology cGAMP follicular helper T cells germinal center Germinal Center - immunology Germinal Center - metabolism Lymphocyte Activation - immunology Membrane Proteins - immunology Membrane Proteins - metabolism Mice Mice, Inbred C57BL Nucleotides, Cyclic - immunology Nucleotides, Cyclic - metabolism plasma cells Plasma Cells - immunology Plasma Cells - metabolism Signal Transduction STING ligand STING ligand germinal center cGAMP follicular helper T cells plasma cells
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Summary:	Germinal center (GC) responses are essential for establishing protective, long-lasting immunity through the differentiation of GC B cells (B ) and plasma cells (B ), along with the generation of antigen-specific antibodies. Among the various pathways influencing immune responses, the STING (Stimulator of Interferon Genes) pathway has emerged as significant, especially in innate immunity, and extends its influence to adaptive responses. In this study, we examined how the STING ligand cGAMP can modulate these key elements of the adaptive immune response, particularly in enhancing GC reactions and the differentiation of B , B , and follicular helper T cells (T ). Employing models, we evaluated various antigens and the administration of cGAMP in Alum adjuvant, investigating the differentiation of B , B , and T cells, along with the production of antigen-specific antibodies. cGAMP enhances the differentiation of B and B , leading to increased antigen-specific antibody production. This effect is shown to be type I Interferon-dependent, with a substantial reduction in B frequency upon interferon (IFN)-β blockade. Additionally, cGAMP's influence on T differentiation varies over time, which may be critical for refining vaccine strategies. The findings elucidate a complex, antigen-specific influence of cGAMP on T and B cell responses, providing insights that could optimize vaccine efficacy.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1664-3224 1664-3224
DOI:	10.3389/fimmu.2024.1340001