A new paradigm of T cell allergy: Requirement for the B-1 cell subset

Background: We have uncovered a role for B-1-B-cell-produced IgM antibody, in the initiation of contact sensitivity (CS) in mice. CS and delayed-type hypersensitivity (DTH) involve recruitment of T cells to the tissues, to be activated by antigen-presenting cells (APC), and then make cytokines. Litt le is known about low recruitment is initiated. In CS, soon after immunizat ion, the unique B-l cell subset, responsible for the formation of most IgM, is activated to produce antigen (Ag)-specific IgM for export to tissues. I gM forms complexes with challenge Ag, activating the classical complement ( C) pathway, generating C5a, to activate endothelium directly, or indirectly via C5a receptors (R) on mast cells and platelets, that release vasoactive amines (serotonin) and cytokines (TNF-a). These act together to induce vas odilatation, vascular permeability and expression of endothelial adhesion m olecules to promote optimal T cell recruitment. Methods and Results: New fi ndings that established this pathway include: (1) absent CS response in C-d eficient, or C-inhibited mice; (2) local generation of C5a in CS tissue ext racts; (3) absent CS in C5aR-/- mice; (4) decreased CS in B cell and B-l-ce ll-deficient mice, and (5) reconstitution of CS by transfer of B-l cells, o r hapten-specific IgM. Conclusion: These findings indicate that the B-l sub set producing Ag-specific IgM is required early in CS to activate C, to ind uce vasoactive mediators that initiate local T recruitment.