title: Subunits of IgM reconstitute defective contact sensitivity in B-1 cell-deficient xid mice: kappa light chains recruit T cells independent of complement.
abstract: 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.
authors.affiliation: Section of Allergy and Clinical Immunology, Department of Internal Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
authors.forename: Vipin
authors.initials: V
authors.lastname: Paliwal
authors.forename: Ryohei F
authors.initials: RF
authors.lastname: Tsuji
authors.forename: Marian
authors.initials: M
authors.lastname: Szczepanik
authors.forename: Ivana
authors.initials: I
authors.lastname: Kawikova
authors.forename: Regis A
authors.initials: RA
authors.lastname: Campos
authors.forename: Manfred
authors.initials: M
authors.lastname: Kneilling
authors.forename: Martin
authors.initials: M
authors.lastname: Röcken
authors.forename: Janine
authors.initials: J
authors.lastname: Schuurman
authors.forename: Frank A
authors.initials: FA
authors.lastname: Redegeld
authors.forename: Frans P
authors.initials: FP
authors.lastname: Nijkamp
authors.forename: Philip W
authors.initials: PW
authors.lastname: Askenase
mesh_terms: 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
chemical_list: D006241:Haptens; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains; D021122:Protein Subunits; D014301:Trinitrobenzenes; D003165:Complement System Proteins