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2014-7-29

A group of researchers from Osaka University, Riken, Tokyo University of Science, and Tulane University have demonstrated in experiments using mice that major immune cells responsible for immune memory: memory B-cells and memory T cells (follicular helper T (TFH) cells) residing close to each other quickly interacted with each other, thereby inducing rapid recall antibody response.

KUROSAKI Tomohiro, Professor, Immunology Frontier Research Center, Osaka University; Group Director, Center for Integrative Medical Sciences, Riken

One of the most important immune responses is one in which B cells produce antibodies in order to remove antigens. This antibody response in the secondary immune response is stronger and faster than that in the primary immune response. This is known as a memory immune response and is utilized in vaccine therapy. Memory B- and T- cells are responsible for such memory immune responses. Generally, T cells are needed for B cells to produce antibodies. TFH cells help B cells produce antibodies; however, whether TFH cells are involved in antibody response by memory B cells and if so, how TFH cells are activated has been unknown.This group's research has clarified that direct interaction between memory T cells and memory B cells induced efficient memory immune responses (memory antibody responses). Since memory TFH cells work as key players in these memory antibody responses, the efficient induction of memory TFH cells will lead to the possible development of vaccines for greater production of antibodies.

Abstract

In primary humoral responses, B-cell lymphoma 6 (Bcl6) is a master regulator of follicular helper T (TFH) cell differentiation; however, its activation mechanisms and role in memory responses remain unclear. Here we demonstrate that survival of CXCR5+ TFH memory cells, and thus subsequent recall antibody response, require Bcl6 expression. Furthermore, we show that, upon rechallenge with soluble antigen Bcl6 in memory TFH cells is rapidly induced in a dendritic cell-independent manner and that peptide:class II complexes (pMHC) on cognate memory B cells significantly contribute to this induction. Given the previous evidence that antigen-specific B cells residing in the follicles acquire antigens within minutes of injection, our results suggest that memory B cells present antigens to the cognate TFH memory cells, thereby contributing to rapid Bcl6 reexpression and differentiation of the TFH memory cells during humoral memory responses.

 

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To learn more about this research, please view the full research report entitled "Memory B cells contribute to rapid Bcl6 expression by memory follicular helper T cells" at this page of the Proceedings of the National Academy of Sciences website.



Related link:

Lab of Lymphocyte Differentiation, Immunology Frontier Research Center, Osaka University

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