The Omentum Is a Site of Protective IgM Production during Intracellular Bacterial Infection

Abstract

Infection of mice with the bacterium Ehrlichia muris elicits a protective T cell-independent (TI) IgM response mediated primarily by a population of CD11c-expressing plasmablasts in the spleen. Although splenic marginal zone (MZ) B cells are considered to be important for TI responses to blood-borne pathogens, MZ B cells were not responsible for generating plasmablasts in response to Ehrlichia muris. Moreover, antigen-specific serum IgM was decreased only modestly in splenectomized mice and in mice that lacked spleen, lymph nodes, and Peyer's patches (SLP mice). Both splenectomized and SLP mice were protected against lethal ehrlichial challenge infection. Moreover, we found a high frequency of Ehrlichia-specific plasmablasts in the omentum of both conventional and SLP mice. Omental plasmablasts elicited during Ehrlichia infection lacked expression of CD138 but expressed CD11c in a manner similar to that of their splenic counterparts. Selective ablation of CD11c-expressing B cells nearly eliminated the omental Ehrlichia-specific plasmablasts and reduced antigen-specific serum IgM, identifying the omental B cells as a source of IgM production in the SLP mice. Generation of the omental plasmablasts was route dependent, as they were detected following peritoneal infection but not following intravenous infection. Our data identify the omentum as an important auxiliary site of IgM production during intracellular bacterial infection.

Immunological Functions of the Omentum

“…Interestingly, the IL-33-induced expression of IL-5 by ILC2 cells in the FALCs of the pericardium promotes the differentiation of local B1 B cells into IgM-secreting cells [15]. Given that ILC2 cells are also present in the omentum, a similar process likely occurs in this location [47]. ILC2 cells also help regulate metabolic functions.…”

“…Peritoneal administration of LPS also promotes the migration of peritoneal B1 cells to the MS [50, 51, 61], where they differentiate into IgM-secreting and IgA-secreting cells, some of which colonize the intestine [67, 68], possibly by CXCR4-dependent mechanisms [69]. The omentum also supports the formation and local maintenance of IgM + memory B cells and CD11c + IgM plasmablasts in response to peritoneal infection [47]. Importantly, LPS-mediated peritoneal inflammation triggers the rapid accumulation of GATA6+ macrophages in the omentum, which produce RA [50, 51], a key factor in isotype switching to IgA [52, 53].…”

“…Nevertheless, T-dependent B cell responses in MS lead to high titers of antigen-specific serum IgG [9]. Importantly, these can occur in mice lacking conventional secondary lymphoid organs (Spleen, Lymph node and Peyer’s patch-deficient — SLP mice) [47]. Thus, although some might argue that the primary purpose of the MS is to support the rapid differentiation of B1 cells into IgM and IgA-secreting cells, conventional, T-dependent B cell responses also occur in these sites.…”

Specific Biological Features of Adipose Tissue, and Their Impact on HIV Persistence

“…It is not yet clear whether MSs and FALCs are different immune clusters (they can differ in their composition and size) (Moro et al, 2010;Lolmède et al, 2011;Meza-Perez and Randall, 2017;Bénézech and Jackson-Jones, 2019), although both have immune functions (Rangel-Moreno et al, 2009;Bénézech and Jackson-Jones, 2019). Group 2 innate lymphoid cells (ILC2s) and B cells are crucial components of FALCs, since they coordinate local immune responses in fat depots and contribute to AT homeostasis (Bénézech and Jackson-Jones, 2019) and anti-infectious responses (Jones et al, 2015). These immune clusters provided the first evidence of a direct role of fat immune cells in anti-infectious responses, and also highlight the "regionalization" of AT.…”

Patient-derived xenografts of low-grade B-cell lymphomas demonstrate roles of the tumor microenvironment

“…6,7 An adipose-rich, highly vascularized structure, the omentum is a key organ for lymphocyte trafficking to and from the peritoneal cavity, potentially accounting for the preferential engraftment of human immune cells at this site. 8 Here,…”