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. Little is known about low recruitment is initiated. In CS, soon after immunization, the unique B-1 cell subset, responsible for the formation of most IgM, is activated to produce antigen (Ag)-specific IgM for export to tissues. IgM 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-alpha). These act together to induce vasodilatation, vascular permeability and expression of endothelial adhesion molecules to promote optimal T cell recruitment.


RESULTS
New findings that established this pathway include: (1) absent CS response in C-deficient, or C-inhibited mice; (2) local generation of C5a in CS tissue extracts; (3) absent CS in C5aR-/- mice; (4) decreased CS in B cell and B-1-cell-deficient mice, and (5) reconstitution of CS by transfer of B-1 cells, or hapten-specific IgM.


CONCLUSIONS
These findings indicate that the B-1 subset producing Ag-specific IgM is required early in CS to activate C, to induce vasoactive mediators that initiate local T recruitment.
Askenase
P W
PW
Section of Allergy and Clinical Immunology, Department of Medicine, Yale University School of Medicine, New Haven, CT, USA. Askenase.lab@qm.Yale.edu
Kawikova
I
I
Paliwal
V
V
Akahira-Azuma
M
M
Gerard
C
C
Hugli
T
T
Tsuji
R
R
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D003877:Dermatitis, Contact / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology*; D008211:Lymphocyte Cooperation / Q000276:immunology; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*
D007075:Immunoglobulin M