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Publication : Extrafollicular B cell activation by marginal zone dendritic cells drives T cell-dependent antibody responses.

First Author  Chappell CP Year  2012
Journal  J Exp Med Volume  209
Issue  10 Pages  1825-40
PubMed ID  22966002 Mgi Jnum  J:191423
Mgi Id  MGI:5461747 Doi  10.1084/jem.20120774
Citation  Chappell CP, et al. (2012) Extrafollicular B cell activation by marginal zone dendritic cells drives T cell-dependent antibody responses. J Exp Med 209(10):1825-40
abstractText  Dendritic cells (DCs) are best known for their ability to activate naive T cells, and emerging evidence suggests that distinct DC subsets induce specialized T cell responses. However, little is known concerning the role of DC subsets in the initiation of B cell responses. We report that antigen (Ag) delivery to DC-inhibitory receptor 2 (DCIR2) found on marginal zone (MZ)-associated CD8alpha(-) DCs in mice leads to robust class-switched antibody (Ab) responses to a T cell-dependent (TD) Ag. DCIR2(+) DCs induced rapid up-regulation of multiple B cell activation markers and changes in chemokine receptor expression, resulting in accumulation of Ag-specific B cells within extrafollicular splenic bridging channels as early as 24 h after immunization. Ag-specific B cells primed by DCIR2(+) DCs were remarkably efficient at driving naive CD4 T cell proliferation, yet DCIR2-induced responses failed to form germinal centers or undergo affinity maturation of serum Ab unless toll-like receptor (TLR) 7 or TLR9 agonists were included at the time of immunization. These results demonstrate DCIR2(+) DCs have a unique capacity to initiate extrafollicular B cell responses to TD Ag, and thus define a novel division of labor among splenic DC subsets for B cell activation during humoral immune responses.
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