BLyS drives affinity maturation

I have found an interesting paper that describes in the very detailed way how the interactions between two specialized subsets of lymphocytes which are germinal center (GC) B cells and follicular helper (FH) T cells may influence the affinity maturation of antibodies. The cooperation of these two subsets is known for the long time. However, the novelty this publication brings about is that it looks specifically at the germinal center reaction and dissects the role that the molecule called BLyS (or interchangeably BAFF) may play in the affinity maturation of antibodies from other tasks fulfilled by the same protein. In other words, BLyS has important functions in many aspects of B cells life and the exact definition of its role in the affinity maturation process was not possible using relatively straightforward methods like studying mice with deletion of gene encoding BLyS.

The link: http://jem.rupress.org/content/211/1/45.abstract

Authors perform the study on mice that were immunized with nitrophenacethyl hapten conjugated with chicken gamma globulin which is a widely used method to elicit a strong germinal center reaction. What forms the basis of this paper is the observation that receptor-bound BLyS seems to be selectively excluded form B cells that are located inside germinal centers. Investigators follow with the demonstration that activated B cells downregulate TACI (one of three BLyS receptors), that IL-21 may be responsible for the observed TACI downregulation and finally that in the context of germinal center (and unlike systemically) the main source of BLyS comes from cells of hematopoietic origin, namely follicular helper T cells.

But what role the T cell-derived BLyS may have for the quality of the antibody response? To answer this question authors create an experimental setting (mixed bone marrow chimeras) where the T cell lineage lacks BLyS. In such circumstances germinal centers do form and are maintained mostly normally. However, the ability to form high-affinity antibodies is visibly impaired when germinal centers operate without T-cell derived BLyS.

Radhika Goenka, Andrew H. Matthews, Bochao Zhang, Patrick J. O’Neill, Jean L. Scholz, Thi-Sau Migone, Warren J. Leonard, William Stohl, Uri Hershberg, and Michael P. Cancro (2014). Local BLyS production by T follicular cells mediates retention of high affinity B cells during affinity maturation Journal of Experimental Medicine DOI: 10.1084/jem.20130505

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