Subcapsular encounter and complement-dependent transport of immune complexes by lymph node B cells

Abstract

The mechanism of B cell-antigen encounter in lymphoid tissues is incompletely understood. It is also unclear how immune complexes are transported to follicular dendritic cells. Here, using real-time two-photon microscopy we noted rapid delivery of immune complexes through the lymph to macrophages in the lymph node subcapsular sinus. B cells captured immune complexes by a complement receptor-dependent mechanism from macrophage processes that penetrated the follicle and transported the complexes to follicular dendritic cells. Furthermore, cognate B cells captured antigen-containing immune complexes from macrophage processes and migrated to the T zone. Our findings identify macrophages lining the subcapsular sinus as an important site of B cell encounter with immune complexes and show that intrafollicular B cell migration facilitates the transport of immune complexes as well as encounters with cognate antigen.

A Novel B Cell-Mediated Transport of IgE-Immune Complexes to the Follicle of the Spleen

“…To our knowledge, there are no other reports of such a rapid transport of Ag into the B cell follicle as demonstrated here with IgE/Ag. When localization of IgG-Ag complexes in lymph nodes was studied, most of the Ag remained in the subcapsular sinus 2 h after immunization (37), and hen egg lysozyme (HEL) administered i. v. remained in the MZ of the spleen after 30 min (50). Ag complexed with IgM and C given i. v. was initially found on the surface of MZ B cells, bound to the C receptor CD21.…”

“…The only murine hematopoietic cells expressing CD23 are B cells and FDCs (20 -22). Since CD23 expression on B cells, but not on FDCs, is required for IgE-mediated enhancement (18,19), a mechanism involving transfer of IgE/Ag from FO B cells to FDCs, as shown to take place with IgM-and IgG-immune complexes (37,43) mechanism is CD23 dependent. Especially when using EBV-transformed B cell lines, which should be free of contaminating cell types, contribution of DCs to the T cell stimulation/Ag presentation is excluded (26 -28).…”

“…Specific B cells, located in the folliclesubcapsular sinus boundary of the lymph nodes, also seem to be able to transport Ag into the follicle (36). In addition, macrophages in the subcapsular sinus of lymph nodes can capture IgG-immune complexes and deliver these to the follicle where B cells in a complement-receptor 1/2 (CD35/CD21)-dependent manner transport them to FDCs (37).…”

Expression of complement receptors 1 (CR1/CD35) and 2 (CR2/CD21), and co-signaling molecule CD19 in cattle

“…In addition, cleaved components of the complement cascade have a role in regulating immune responses. Cleaved products can mediate opsonization, chemotaxis of phagocytes, mast cell degranulation, antigen transportation to germinal centers (Phan et al, 2007;Phan et al, 2009), as well as regulating signaling by Toll--like receptors (Hajishengallis & Lambris, 2010). These cleaved products also affect activation of the adaptive immune system in jawed vertebrates.…”

“…Failure of this transport in Cr2--/--mice is associated with decreased afBinity maturation (Phan et al, 2007;Phan et al, 2009)…”