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Subunits of IgM Reconstitute Defective Contact Sensitivity in B-1 Cell-Deficient xid Mice: Light Chains Recruit T Cells Independent of Complement¹

Vipin Paliwal^*, Ryohei F. Tsuji, Marian Szczepanik, Ivana Kawikova^*, Regis A. Campos^*, Manfred Kneilling^¶, Martin Röcken^¶, Janine Schuurman, Frank A. Redegeld, Frans P. Nijkamp and Philip W. Askenase^2,*

^* Section of Allergy and Clinical Immunology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520; Noda Institute for Scientific Research, Chiba-ken, Japan; Department of Immunology, Jagiellonian University College of Medicine, Krakow, Poland; Department of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands; and ^¶ Department of Dermatology and Allergology, Ludwig-Maximillians-University, Munich, Germany

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 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 L chains act via another C-independent but mast cell-dependent pathway.

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