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. |