Subunits of IgM reconstitute defective contact sensitivity in B-1 cell-deficient xid mice: kappa light chains recruit T cells independent of complement.
The elicitation of contact sensitivity (CS) to local skin challenge with the hapten trinitrophenyl (TNP) chloride requires an early process that is necessary for local recruitment of CS-effector T cells. This is called CS initiation and is due to the B-1 subset of B cells activated at immunization to produce circulating IgM Ab. At challenge, the IgM binds hapten Ag in a complex that locally activates C to generate C5a that aids in T cell recruitment. In this study, we present evidence that CS initiation is indeed mediated by C-activating classic IgM anti-TNP pentamer. We further demonstrate the involvement of IgM subunits derived either from hybridomas or from lymphoid cells of actively immunized mice. Thus, reduced and alkylated anti-TNP IgM also initiates CS, likely due to generated H chain-L chain dimers, as does a mixture of separated H and L chains that still could weakly bind hapten, but could not activate C. Remarkably, anti-TNP kappa L chains alone mediated CS initiation that was C-independent, but was dependent on mast cells. Thus, B-1 cell-mediated CS initiation required for T cell recruitment is due to activation of C by specific IgM pentamer, and also subunits of IgM, while kappa L chains act via another C-independent but mast cell-dependent pathway.
Paliwal
Vipin
V
Section of Allergy and Clinical Immunology, Department of Internal Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
Tsuji
Ryohei F
RF
Szczepanik
Marian
M
Kawikova
Ivana
I
Campos
Regis A
RA
Kneilling
Manfred
M
Röcken
Martin
M
Schuurman
Janine
J
Redegeld
Frank A
FA
Nijkamp
Frans P
FP
Askenase
Philip W
PW
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000473:pathology*; D001666:Binding Sites, Antibody / Q000235:genetics; D003167:Complement Activation / Q000235:genetics / Q000276:immunology; D003165:Complement System Proteins / Q000502:physiology*; D003877:Dermatitis, Contact / Q000235:genetics / Q000276:immunology*; D019281:Dimerization; D004431:Ear, External / Q000276:immunology; D004487:Edema / Q000235:genetics / Q000276:immunology; D005260:Female; D006241:Haptens / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D007075:Immunoglobulin M / Q000008:administration & dosage / Q000378:metabolism*; D007145:Immunoglobulin kappa-Chains / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology / Q000502:physiology*; D007275:Injections, Intravenous; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains; D021122:Protein Subunits; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014301:Trinitrobenzenes / Q000276:immunology
D006241:Haptens; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains; D021122:Protein Subunits; D014301:Trinitrobenzenes; D003165:Complement System Proteins