Cutting Edge: LL-37–Mediated Formyl Peptide Receptor-2 Signaling in Follicular Dendritic Cells Contributes to B Cell Activation in Peyer’s Patch Germinal Centers

We investigated the mechanism of CD4 T cell accumulation in B cell follicles after immunization. Follicular T cell numbers were correlated with the number of B cells, indicating B cell control of the niche that T cells occupy. Despite this, we found no role for B cells in the follicular migration of T cells. Instead, T cells are induced to migrate into B cell follicles entirely as a result of interaction with dendritic cells (DCs). Migration relies on CD40-dependent maturation of DCs, as it did not occur in CD40-deficient mice but was reconstituted with CD40+ DCs. Restoration was not achieved by the activation of DCs with bacterial activators (e.g., lipopolysaccharide, CpG), but was by the injection of OX40L–huIgG1 fusion protein. Crucially, the up-regulation of OX40L (on antigen-presenting cells) and CXCR-5 (on T cells) are CD40-dependent events and we show that T cells do not migrate to follicles in immunized OX40-deficient mice.

Download Full-text

Extrafollicular B cell activation by marginal zone dendritic cells drives T cell–dependent antibody responses

Journal of Experimental Medicine ◽

10.1084/jem.20120774 ◽

2012 ◽

Vol 209 (10) ◽

pp. 1825-1840 ◽

Cited By ~ 67

Author(s):

Craig P. Chappell ◽

Kevin E. Draves ◽

Natalia V. Giltiay ◽

Edward A. Clark

Keyword(s):

Dendritic Cells ◽

T Cell ◽

B Cells ◽

B Cell ◽

Cell Activation ◽

Marginal Zone ◽

Receptor Expression ◽

B Cell Activation ◽

Cell Responses ◽

B Cell Responses

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 CD8α− 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.

Download Full-text

Lineage-Restricted Function of Nuclear Factor κB–Inducing Kinase (Nik) in Transducing Signals via Cd40

Journal of Experimental Medicine ◽

10.1084/jem.191.2.381 ◽

2000 ◽

Vol 191 (2) ◽

pp. 381-386 ◽

Cited By ~ 50

Author(s):

Norman Garceau ◽

Yoko Kosaka ◽

Sally Masters ◽

John Hambor ◽

Reiko Shinkura ◽

...

Keyword(s):

Dendritic Cells ◽

B Cells ◽

B Cell ◽

Cell Activation ◽

Nuclear Factor Κb ◽

Cell Mediated Immunity ◽

Nuclear Factor ◽

Compelling Evidence ◽

B Cell Activation

CD40 signaling in B cells and dendritic cells (DCs) is critical for the development of humoral and cell-mediated immunity, respectively. Nuclear factor κB (NF-κB)–inducing kinase (NIK) has been implicated as a central transducing kinase in CD40-dependent activation. Here, we show that although NIK is essential for B cell activation, it is dispensable for activation of DCs. Such data provide compelling evidence that different intermediary kinases are used by different cellular lineages to trigger NF-κB activation via CD40.

Download Full-text