Human Dendritic Cells Skew Isotype Switching of CD40-activated Naive B Cells towards IgA1 and IgA2

Abstract

Within T cell–rich areas of secondary lymphoid organs, interdigitating dendritic cells recruit antigen-specific T cells that then induce B cells to secrete Igs. This study investigates the possible role(s) of dendritic cells in the regulation of human B cell responses. In the absence of exogenous cytokines, in vitro generated dendritic cells (referred to as Dendritic Langerhans cells, D-Lc) induced surface IgA expression on ∼10% of CD40-activated naive sIgD+ B cells. In the presence of IL-10 and TGF-β, a combination of cytokines previously identified for its capacity to induce IgA switch, D-Lc strongly potentiated the induction of sIgA on CD40-activated naive B cells from 5% to 40–50%. D-Lc alone did not induce the secretion of IgA by CD40-activated naive B cells, which required further addition of IL-10. Furthermore, D-Lc skewed towards the IgA isotype at the expense of IgG, the Ig production of CD40-activated naive B cells cultured in the presence of IL-10 and TGF-β. Importantly, under these culture conditions, both IgA1 and IgA2 were detected. In the presence of IL-10, secretion of IgA2 by CD40-activated naive B cells could be detected only in response to D-Lc and was further enhanced by TGF-β. Collectively, these results suggest that in addition to activating T cells in the extrafollicular areas of secondary lymphoid organs, human D-Lc also directly modulate T cell–dependent B cell growth and differentiation, by inducing the IgA isotype switch.

Apoptosis Induced by TGF-β1 in Burkitt’s Lymphoma Cells Is Caspase 8 Dependent But Is Death Receptor Independent

“…Follicular dendritic cells, which are present in germinal center regions, produce bioactive TGF-␤1 (10). Recently, it was demonstrated that dendritic cells can promote class switching of naive CD40-triggered human B cells to an IgA phenotype in the presence of IL-10, and that this process is partially dependent on endogenous TGF-␤1 (67). It is has also been reported that TGF-␤1 may cause apoptosis in human B cells isolated from tonsil, preparations that contain germinal center B cells (20).…”

Local and Systemic Effects of Intranodally Injected CpG-C Immunostimulatory-Oligodeoxyribonucleotides in Macaques

“…Pathogen-derived components and/or proinflammatory stimuli induce DCs to mature and migrate into lymphoid tissue or lymph nodes (LNs) where, as interdigitating DCs, they form a network in the parafollicular T cell-rich areas and orchestrate immune responses. Increasing evidence indicates how DCs and B cells also communicate with each other to encourage potent Th1 immunity (5)(6)(7)(8)(9)(10)(11)(12). Strategies that boost DC and B cell functions should improve prophylactic and therapeutic vaccines against pathogens like HIV.…”

Porcine Antigen Presenting Cells Produce Soluble Adjuvants That Stimulate B cells Within and Across the Species

“…We have not, to this point, characterized the ability of fully matured pDCs to stimulate B cells. Nonetheless, the observation that inclusion of pIL-4 (which did enhance APC maturity compared with pGM- (9)(10)(11)(12). In in vivo experiments conducted in the rat, DCs were observed to acquire antigen in the spleen, retain it for at least 48 h in a native form, and present it to B cells along with signals involved in isotype switching to antigen-specific B cells via direct contact (13).…”

“…These interactions, which include T-cell-derived cytokines and the ligation of CD40 on B cells by its ligand CD154 on T cells, represent the indirect effects of mature APCs on humoral immunity (7,8). In addition, however, a more direct dialogue between DCs and B cells exists (9)(10)(11)(12)(13). Studies have provided evidence that DCs can directly stimulate the proliferation and differentiation of B cells in combination with other stimuli (9)(10)(11), and can activate naive B cells to initiate the synthesis and class-switching of antibodies (12,13).…”