B Cell‐mediated Antigen Transport to Splenic Follicles

An effective antibody response requires that antibodies go through affinity maturation and class switch recombination. These reactions largely take place in germinal centres which develop in B cell follicles of secondary lymphoid organs. An important step in this process is antigen deposition on follicular dendritic cells (FDC). Antigen can be transported from the periphery to follicles either via small channels (conduits) or bound to various cell types 1, 2. Generally, antigen transport in lymph nodes is better understood than in the spleen, mostly because lymph nodes are more accessible to visualization. Here, we highlight recent observations which demonstrate that antigens can enter splenic follicles with the help of B cells in three different ways: via the low-affinity receptor for IgE (CD23) 3, via the B cell receptor (BCR) 4 and via the complement receptors CD21/CD35 5, 6 (Fig. 1). Marginal zone (MZ) B cells, only residing in spleen and not in lymph nodes, continuously shuttle between the MZ and the follicles with as much as a 20% exchange of cells between the two compartments per hour 7, 8. MZ B cells express high levels of CD21/CD35. The shuttling takes place independently of whether these receptors are ligated. Once complement-opsonized immune complexes are present in the MZ, they will bind to MZ B cells and be delivered to FDC 5, 6. Whereas MZ B cells require that antigen first be transported to the MZ, recirculating B cells survey the periphery and migrate to secondary lymphoid organs where they reside for approximately one day before returning to the circulation. Hence, it would seem beneficial for the immune system to utilize them for antigen transport, and indeed, two such situations have been described. First, B cells in the blood can capture IgE–antigen complexes via CD23 and rapidly transport them to splenic follicles 3. Subsequently, a potent germinal centre response, massive proliferation of specific CD4+ T cells and a specific IgG response developed 3, 9, 10. As CD23 is a C-type lectin and other receptors of this family are pattern recognition receptors, hypothetically CD23 could bind directly to certain pathogens without using IgE antibodies as a bridge. Second, antigens from the respiratory tract can reach the spleen bound to cognate B cells 4. Twenty-four hours after intranasal administration, viruslike particles were found in splenic B cell follicles, but not in other areas of the spleen. Free viruslike particles in blood were scarce, but four hours after immunization, they were detected on circulating B cells in the blood. Binding occurred via low-affinity BCRs without involvement of CD21/CD35 or FcγRIIB and deposition of antigen in follicles was followed by development of germinal centres and a potent IgG response. These examples of B cell-mediated antigen transport may only be the beginning of identification of a number of pathogens that can bind to circulating B cells and quickly be transported to the splenic follicles.