CD40 signaling drives B lymphocytes into an intermediate memory-like state, poised between naïve and plasma cells.

Autor: Upadhyay M; Centre for Cellular and Molecular Biology, Hyderabad, 500007, India., Priya GK, Ramesh P, Madhavi MB, Rath S, Bal V, George A, Vaidya T
Jazyk: angličtina
Zdroj: Journal of cellular physiology [J Cell Physiol] 2014 Oct; Vol. 229 (10), pp. 1387-96.
DOI: 10.1002/jcp.24572
Abstrakt: Immunological memory comprising of antigen-specific B and T cells contributes to the acquisition of long-term resistance to pathogens. Interactions between CD40 on B cells and CD40L on T cells are responsible for several aspects of acquired immune responses including generation of memory B cells. In order to gain insights into events leading to memory B cell formation, we analyzed the genome-wide expression profile of murine naive B cells stimulated in the presence of anti-CD40. We have identified over 8,000 genes whose expression is altered minimally 1.5-fold at least at one time point over a 3-day time course. The array analysis indicates that changes in expression level of maximum number of these genes occur within 24 h of anti-CD40 treatment. In parallel, we have studied the events following CD40 ligation by examining the expression of known regulators of naive B cell to plasma cell transition, including Pax5 and BLIMP1. The expression profile of these regulatory genes indicates firstly, that CD40 signaling activates naïve B cells to a phenotype that is intermediate between the naive and plasma cell stages of the B cell differentiation. Secondly, the major known regulator of plasma cell differentiation, BLIMP1, gets irreversibly downregulated upon anti-CD40 treatment. Additionally, our data reveal that CD40 signaling mediated BLIMP1 downregulation occurs by non-Pax5/non-Bcl6 dependent mechanisms, indicating novel mechanisms at work that add to the complexity of understanding of B cell master regulatory molecules like BLIMP1 and Pax5.
(© 2014 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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