B cell-deficient (mu MT) mice have alterations in the cytokine microenvironment of the gut-associated lymphoid tissue (GALT) and a defect in the low dose mechanism of oral tolerance.
Peripheral immune tolerance following i.v. administration of Ag has been shown to occur in the absence of B cells. Because different mechanisms have been identified for i.v. vs low dose oral tolerance and B cells are a predominant component of the gut-associated lymphoid tissue (GALT) they may play a role in tolerance induction following oral Ag. To examine the role of B cells in oral tolerance we fed low doses of OVA or myelin oligodendrocyte glycoprotein to B cell-deficient ( microMT) and wild-type C57BL/6 mice. Results showed that the GALT of naive wild-type and microMT mice was characterized by major differences in the cytokine microenvironment. Feeding low doses of 0.5 mg OVA or 250 microg myelin oligodendrocyte glycoprotein resulted in up-regulation of IL-4, IL-10, and TGF-beta in the GALT of wild-type but not microMT mice. Upon stimulation of popliteal node cells, in vitro induction of regulatory cytokines TGF-beta and IL-10 was observed in wild-type but not microMT mice. Greater protection against experimental autoimmune encephalomyelitis was found in wild-type mice. Oral tolerance in microMT and wild-type mice was found to proceed by different mechanisms. Anergy was observed from 0.5 mg to 250 ng in microMT mice but not in wild-type mice. Increased Ag was detected in the lymph of microMT mice. No cytokine-mediated suppression was found following lower doses from 100 ng to 500 pg in either group. These results demonstrate the importance of the B cell for the induction of cytokine-mediated suppression associated with low doses of Ag.
Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. gonnella@cnd.bwh.harvard.edu
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Gonnella
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Waldner
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HL
Weiner
D000284:Administration, Oral; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis* / Q000502:physiology; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D007108:Immune Tolerance / Q000235:genetics; D007148:Immunoglobulin mu-Chains / Q000235:genetics*; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008196:Lymph / Q000737:chemistry / Q000276:immunology; D008198:Lymph Nodes / Q000737:chemistry / Q000276:immunology; D008221:Lymphoid Tissue / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008231:Lymphopenia / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D013045:Species Specificity; D013897:Thoracic Duct / Q000276:immunology
D016207:Cytokines; D007148:Immunoglobulin mu-Chains; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D010047:Ovalbumin