title: In old BALB/c mice, bone marrow pre-B cell and surrogate light chain reduction is associated with increased B cell reactivity to phosphorylcholine, but reduced T15 idiotype dominance.
abstract: In young adult BALB/c mice, antibodies to phosphorylcholine (PC) bearing the T15 (TEPC 15) idiotype confer protection against pneumococcal infections. In old age, even though PC reactive B cells are often increased, the proportion of T15+antibodies declines. We hypothesize that limited surrogate light chain (SLC) and compromise of the pre-B cell receptor checkpoint in old mice contribute to both reduced new B cell generation and changes in the anti-PC antibodies seen in old age. In old mice: 1) early pre-B cell loss is most pronounced at the preBCR checkpoint; however, the reduced pool of early pre-B cells continues to proliferate consistent with preBCR signaling; 2) increased PC reactivity is seen in bone marrow immature B cells; 3) deficient SLC promotes increased B cell PC reactivity and diminished T15 idiotype expression; and 4) as pre-B cell losses and reduced SLC become progressively more severe, increased T15 negative PC reactive B cells occur. These results associate a reduction in pre-B cells, imposed at the preBCR checkpoint, with increased reactivity to PC, but more limited expression of the protective T15 idiotype among PC reactive antibodies in old age.
authors.affiliation: Department of Microbiology & Immunology, University of Miami Miller School of Medicine, Miami, FL, 33136, United States.
authors.forename: Kelly
authors.initials: K
authors.lastname: Khomtchouk
authors.affiliation: Department of Microbiology & Immunology, University of Miami Miller School of Medicine, Miami, FL, 33136, United States.
authors.forename: Sarah
authors.initials: S
authors.lastname: Alter
authors.affiliation: Department of Microbiology & Immunology, University of Miami Miller School of Medicine, Miami, FL, 33136, United States.
authors.forename: Michelle
authors.initials: M
authors.lastname: Ratliff
authors.affiliation: Department of Microbiology & Immunology, University of Miami Miller School of Medicine, Miami, FL, 33136, United States.
authors.forename: Bonnie B
authors.initials: BB
authors.lastname: Blomberg
authors.affiliation: Department of Microbiology & Immunology, University of Miami Miller School of Medicine, Miami, FL, 33136, United States. Electronic address: rriley@med.miami.edu.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Riley
mesh_terms: D000375:Aging / Q000276:immunology* / Q000473:pathology; D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology* / Q000473:pathology; D007147:Immunoglobulin Light Chains / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010767:Phosphorylcholine / Q000276:immunology*; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology* / Q000473:pathology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
chemical_list: D001323:Autoantibodies; D007147:Immunoglobulin Light Chains; D011947:Receptors, Antigen, B-Cell; D010767:Phosphorylcholine
keywords: Aging; Immature B cells; Phosphorylcholine; Pre-B cell receptor; Surrogate light chain; T15 idiotype