B-1 B cells mediate required early T cell recruitment to elicit protein-induced delayed-type hypersensitivity.
We define the initiation of elicited delayed-type hypersensitivity (DTH) as a series of processes leading to local extravascular recruitment of effector T cells. Responses thus have two sequential phases: 1) 2-h peaking initiation required for subsequent recruitment of T cells, and 2) the late classical 24-h component mediated by the recruited T cells. We analyzed DTH initiation to protein Ags induced by intradermal immunization without adjuvants. Ag-spceific initiating cells are present by 1 day in spleen and lymph nodes. Their phenotypes, determined by depletion of cell transfers by mAb and complement, are CD5(+), CD19(+), CD22(+), B220(+), Thy1(+), and Mac1(+), suggesting that they are B-1 B cells. DTH initiation is absent in micro MT B cell and xid B-1 cell deficient mice, is impaired in mice unable to secrete IgM, and is reconstituted with 1 day immune serum, suggesting that early B-1 cell-derived IgM is responsible. Study of complement C5a receptor-deficient mice, anti-C5 mAb neutralization, or mast cell deficiency suggests that DTH initiation depends on complement and mast cells. ELISPOT assay confirmed production of Ag-specific IgM Abs at days 1 and 4 in wild-type mice, but not in B-1 cell-deficient xid mice. We conclude that rapidly activated B-1 cells produce specific IgM Abs which, after local secondary skin challenge, form Ag-Ab complexes that activate complement to generate C5a. This stimulates C5a receptors on mast cells to release vasoactive substances, leading to endothelial activation for the 2-h DTH-initiating response, allowing local recruitment of DTH-effector T cells.
Szczepanik
Marian
M
Department of Human Developmental Biology, Jagiellonian University College of Medicine, Krakow, Poland.
Akahira-Azuma
Moe
M
Bryniarski
Krzysztof
K
Tsuji
Ryohei F
RF
Kawikova
Ivana
I
Ptak
Wlodzimierz
W
Kiener
Claudia
C
Campos
Regis A
RA
Askenase
Philip W
PW
D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D003182:Complement C5 / Q000502:physiology; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006433:Hemocyanins / Q000008:administration & dosage / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007144:Immunoglobulin J-Chains / Q000235:genetics; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000502:physiology; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D008212:Lymphocyte Depletion; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D044087:Receptor, Anaphylatoxin C5a / Q000502:physiology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology*; D013997:Time Factors
D000941:Antigens; D003182:Complement C5; D018984:Epitopes, T-Lymphocyte; D007143:Immunoglobulin Heavy Chains; D007144:Immunoglobulin J-Chains; D007075:Immunoglobulin M; D044087:Receptor, Anaphylatoxin C5a; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin