title: Immunoglobulin class switching appears to be regulated by B-cell antigen receptor-specific T-cell action.
abstract: Antigen affinity is commonly viewed as the driving force behind the selection for dominant clonotypes that can occur during the T-cell-dependent processes of class switch recombination (CSR) and immune maturation. To test this view, we analyzed the variable gene repertoires of natural monoclonal antibodies to the hapten 2-phenyloxazolone (phOx) as well as those generated after phOx protein carrier-induced thymus-dependent or Ficoll-induced thymus-independent antigen stimulation. In contrast to expectations, the extent of IgM heterogeneity proved similar and many IgM from these three populations exhibited similar or even greater affinities than the classic Ox1 clonotype that dominates only after CSR among primary and memory IgG. The population of clones that were selected during CSR exhibited a reduced VH/VL repertoire that was enriched for variable domains with shorter and more uniform CDR-H3 lengths and almost completely stripped of variable domains encoded by the large VH1 family. Thus, contrary to the current paradigm, T-cell-dependent clonal selection during CSR appeared to select for VH family and CDR-H3 loop content even when the affinity provided by alternative clones exhibited similar to increased affinity for antigen.
authors.affiliation: Biochemical Institute, Medical Faculty, Christian-Albrechts-Universität at Kiel, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Lange
authors.forename: Oliver
authors.initials: O
authors.lastname: Hecht
authors.forename: Michael
authors.initials: M
authors.lastname: Zemlin
authors.forename: Ahmad
authors.initials: A
authors.lastname: Trad
authors.forename: Radu I
authors.initials: RI
authors.lastname: Tanasa
authors.forename: Harry W
authors.initials: HW
authors.lastname: Schroeder
authors.forename: Hilmar
authors.initials: H
authors.lastname: Lemke
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000235:genetics / Q000276:immunology*; D022801:Complementarity Determining Regions / Q000235:genetics / Q000276:immunology; D005260:Female; D006241:Haptens / Q000276:immunology / Q000494:pharmacology; D017578:Immunoglobulin Class Switching / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D064446:Orexin Receptors; D010080:Oxazoles / Q000276:immunology / Q000494:pharmacology; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology*; D018013:Receptors, Neuropeptide / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: C119678:4-ethoxymethylene-2-phenyl-2-oxazoline-5-one; D058846:Antibodies, Monoclonal, Murine-Derived; D022801:Complementarity Determining Regions; D006241:Haptens; C497459:Hcrtr1 protein, mouse; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D064446:Orexin Receptors; D010080:Oxazoles; D011947:Receptors, Antigen, B-Cell; D018013:Receptors, Neuropeptide