Control of IgE responses

Abstract

Peyer's patches (PP) in germ-free rats (GF) and in the hyper-IgE syndrome patient (HIES) differ from their conventional rat (C) and healthy human (HH) counterparts in that GF rats contained fewer (two-fold) PP and none was detected in HIES. Existing PP in GF rats had reduced cellularity (three-fold) and different B and T cell subsets: high numbers of IgE-bearing (sIgE +) B cells (∼ 15% of total cells), one-half of which also expressed sIgA, were present in GF rat PP while none was detected in C rat PP (<1%). GF rat PP also contained elevated numbers of sIgA + cells and decreased sIgM + cells, with elevated numbers of sThy 1 + RT 7.1 + Ig − T cells (suppressor phenotype) and reduced sThy 1 − RT 7.1 + Ig − T cells (helper phenotype). The cellular composition of GF rat PP was converted to that resembling a C rat within 18 hr after (a) use of standard (unautoclaved) chow; (b) feeding with certain bacteria or “working” bacterial cell wall components (BCWC) and synthetic derivatives, murein, MTP-PE, and norMDP, but not with LPS, core lipid A, or lipoprotein; BCWC had no effect if injected intravenously; or (c) thymectomy. Each procedure resulted in (i) elimination of sIgE + B cells and normalization of the other isotypes, and (ii) loss of T suppressor cells and normalization of T helper cells. After treatments, no sIgE + cells were detected in bone marrow (BM), thymus, other lymphoid organs, or blood. PP were not detected in HIES, although they were present in HH (∼ 10/individual). P blood contained two distinct sIgE + B cell subpopulations (1, 2), the apparent source of which was mesenteric lymph node (MLN), the only organ in which high numbers of these cells (35%) (five nodes examined) were detected; far fewer IgE + cells were found in spleen (<5%), and none was detected in BM, thymus, other LN, or appendix, which was virtually acellular. Virtually no IgE secreting plasma cells were detected in MLN, spleen, appendix, other lymphoid organs, or in gut lamina propria. IgE + B cells in MLN were not detected in follicles (classical B cell areas); instead, they were found in high numbers in the thymus-dependent area and in medulla. Most follicles (>98%) in MLN and spleen contained intercellular IgE complexed to bacterial antigen and/or CD23 (IgE-binding factor? antigen?), but contained no germinal centers. Thus, exposure of GF rats to gut flora and bacterial peptidoglycan components may have resulted in modulation of IgE isotype expression and/or IgE isotype switching, either directly or through mediation of accessory and/or regulatory T cells. The sites in which sIgE + B cells are down-regulated appear to be PP. Absence of PP in HIES suggests absence of the site(s) in which sIgE + B cells are down-regulated, which may contribute to the abnormalities of IgE regulation observed.