B cell-deficient (μMT) 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 (mu MT) and wild-type C57BL/6 mice. Results showed that the GALT of naive wild-type and mu MT mice was characterized by major differences in the cytokine microenvironment. Feeding low doses of 0.5 mg OVA or 250 mug myelin oligodendrocyte glycoprotein resulted in upregulation of IL-4, IL-10, and TGF-beta in the GALT of wild-type but not mu MT 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 mu MT mice. Greater protection against experimental autoimmune encephalomyelitis was found in wild-type mice. Oral tolerance in mu MT and wild-type mice was found to proceed by different mechanisms. Anergy was observed from 0.5 mg to 250 ng in mu MT mice but not in wild-type mice. Increased Ag was detected in the lymph of mu MT 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.