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Eur J Immunol. 2017 Aug;47(8):1295-1304. doi: 10.1002/eji.201746952. Epub 2017 Jul 3.

The strength of BCR signaling shapes terminal development of follicular helper T cells in mice.

Sacquin A1,2,3,4, Gador M1,2,3,4, Fazilleau N1,2,3,4.

Author information

1
Centre de Physiopathologie de Toulouse Purpan, Toulouse, France.
2
INSERM, Toulouse, France.
3
CNRS, Toulouse, France.
4
Université Toulouse III Paul-Sabatier, Toulouse, France.

Abstract

Antibody production is key for effective immune response and relies on follicular helper T (Tfh) cells. B cell-Tfh cell interactions result either in an extra-follicular low affinity B-cell response or in germinal center reactions producing high-affinity memory B cells and long-lived plasma cells. As Tfh cells influence B-cell commitment, it also became clear that B cells influence these interactions in ways that still remain unresolved. We observed that strong BCR signals decreased Tfh-cell differentiation in vitro, which correlated with decreased expression of ICOS-L at the surface of stimulated B cells. Further, we comprehensively demonstrated that ICOS-L expression correlated with the level of Tfh differentiation irrespective of antigen presentation at the surface of activated B cells. Our in vivo experiments could show that immunization with a high-affinity antigen for B cells resulted in much less Tfh development than immunization with low-affinity antigen. Furthermore, blocking ICOS-L in vivo inhibited Tfh development when using low-affinity antigen. Altogether, these results indicate that BCR affinity shapes Tfh-cell development in part through ICOS/ICOS-L interactions. Ultimately, we reveal new depths in the B cell-Tfh cell crosstalk that could eventually result in better vaccine protocols.

KEYWORDS:

Antigen receptors; B cells; BCR; Follicular helper T cells; ICOS-L; Immune responses

PMID:
28605013
DOI:
10.1002/eji.201746952
[Indexed for MEDLINE]
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