Antigens may be delivered to naive B cells in lymphoid organs by multiple routes (Fig. 1). Antigens that elicit antibody responses may vary in size and composition (they may be small, soluble, large, or particulate) and may be free or bound to anti bodies in immune complexes. The major pathways of antigen delivery may vary for different types of antigens.
• Most antigens from tissue sites are transported to lymph nodes by afferent lymphatic vessels that drain into the sub capsular sinus of the nodes. Soluble antigens, generally smaller than 70 kD, may then reach the B-cell zone through conduits that extend between the subcapsular sinus and the underlying follicles.
• Subcapsular sinus macrophages and macrophages in the marginal sinus of the spleen capture complement-coated microbes and antigen-antibody complexes and deliver these to follicles. These macrophages do not internalize and digest the complement-coated particles they bind, thus preserving them on the cell surface for B-cell activation.
• Many antigens that enter the lymph node through afferent lymphatic vessels are not captured by subcapsular sinus macrophages and may be displayed to B cells by dendritic cells (DCs). Although the primary role of DCs is in T-cell activation, studies using live microscopy have shown that when naive B cells pass through the outer T-cell zone on the way to the follicle they can be activated by DCs that continue to display intact protein antigens on the cell surface. How much this contributes to B-cell antigen recognition is unclear.
• Antigens in immune complexes may bind to complement receptors (in particular the complement receptor type 2 [CR2], also called CD21) expressed at high levels on marginal zone B cells, and in the spleen these cells shuttle between the marginal zone and the follicle and can transfer the immune complex–containing antigens to FDCs. Immune complexes bind to CR2 on the surface of FDCs, and the antigens in these complexes may then be presented, often in arrayed form, to antigen-specific B cells. Natural (IgM) antibodies may contribute to the formation of immune complexes and the presentation of some antigens during primary immune responses.
• Polysaccharide antigens can be captured by macrophages in the marginal zone of splenic lymphoid follicles and displayed or transferred to B cells in this area. B-1 cells directly recognize polysaccharide antigens from microbes at mucosal sites and in serosal cavities.
Fig1. Pathways of antigen delivery to follicular B cells. Small antigens are delivered to B cells in follicles through afferent lymphatics and via conduits, and larger antigens by subcapsular sinus macrophages or by dendritic cells in the medulla.
In all these cases, the antigen that is presented to B cells is in its intact, native conformation and has not been processed by antigen-presenting cells. This, of course, is one of the important differences between the forms of antigens recognized by B and T lymphocytes. It is not clear how the various cell types that may display protein antigens to B cells do so without ingesting and degrading the antigens.
