Role of B cells as antigen-presenting cells in vivo revisited: antigen-specific B cells are essential for T cell expansion in lymph nodes and for systemic T cell responses to low antigen concentrations

Abstract

Studies in B cell-deficient mice generated by continuous injection of anti-mu antibodies (muSM) showed that T cell priming in lymph nodes was dependent on antigen presentation by B cells. This concept has recently become controversial since a wide range, from complete deficiency to near normal T cell responses, was reported in studies carried out with B cell-deficient mice generated by gene disruption (muMT). In this study we show that in the absence of B cells, T cell responses are greatly reduced in all the available muMT mouse strains although responses in muMT of the C57BL/6 background (which were used for most studies with muMT) were much more variable and could reach up to 42% of control. In contrast, T cell responses in muMT --> F(1) bone marrow chimeras which have the same phenotype as muMT were totally impaired, suggesting a principle difference between mice developing without B cells (muMT mice) and muSM which are made B cell deficient only after birth. Normal T cell priming was completely restored by reconstitution of muMT and muMT --> F(1) mice with syngeneic B cells. Interestingly, only B cell populations containing antigen-specific B cells were capable of reconstituting T cell responses. Monoclonal B cells taken from Ig transgenic mice could not reconstitute responses to an irrelevant antigen. We also found that B cells were also required for systemic T cell priming when antigen concentrations were limiting but were not required for priming (for T cell help) when mice were immunized with a high antigen dose.

Clearance ofCitrobacter rodentiumRequires B Cells but Not Secretory Immunoglobulin A (IgA) or IgM Antibodies

“…The underlying mechanisms are not known, but B cells play a developmental role in the formation of the intestinal lymphoid tissue (7), which may be important for the detection of bacterial pathogens and for mounting effective immune defenses, even in the absence of a direct B-cell involvement. B cells are also potent antigen-presenting cells (9,30) and have been shown to facilitate the development of effective T-cell responses in host defense against microbial infections (19,42). In addition, B cells can secrete chemotactic cytokines that are important for the recruitment of immune and inflammatory cells (17).…”

Chapter 4 B Cells and Autoantibodies in the Pathogenesis of Multiple Sclerosis and Related Inflammatory Demyelinating Diseases

“…Antigen-specific B and T cells form long-lasting immune synapses characterized by accumulation of peptide-MHC complexes at the site of cell-cell contact (Gordy et al, 2004). The coordination of antigen uptake, class II loading, and costimulatory molecule expression allows antigen-specific B cells to activate cognate T cells far more efficiently than nonspecific B cells or monocytes (Lanzavecchia, 1985), and antigen-specific B cells are required to prime CD4 T cells with low doses of antigen (Rivera et al, 2001). In addition to directly presenting antigens to autoreactive T cells, live B cells can also transfer antigen to macrophages by cell-cell contact, but the precise mechanism of this transfer is unknown (Harvey et al, 2007;Townsend and Goodnow, 1998).…”

Reciprocal generation of Th1/Th17 and Treg cells by B1 and B2 B cells

“…Much effort has been focused on understanding the role and function of dendritic cells (DC) in these processes. Although B cells are also considered professional APC, previous work has focused primarily on their role as terminal effectors of antibody production dependent on the help of DC-primed T cells [1][2][3], whereas their role in T cell priming, differentiation and tolerance has been controversial [4][5][6][7][8].…”