title: A subset of AID-dependent B-1a cells initiates hypersensitivity and pneumococcal pneumonia resistance.
abstract: We propose that there is a special B-1a B cell subset ("sB-1a" cells) that mediates linked processes very early after immunization to initiate cutaneous contact sensitivity (CS), delayed-type hypersensitivity (DTH), and immune resistance to pneumococcal pneumonia. Our published data indicate that in CS and DTH, these initiating processes are required for elicitation of the delayed onset and late-occurring classical T cell-mediated responses. sB-1a cells resemble memory B2 cells, as they are stimulated within 1 h of immunization and depend on T helper cytokines-uniquely IL-4 from hepatic iNKT cells--for activation and rapid migration from the peritoneal cavity to the spleen to secrete IgM antibody (Ab) and Ab-derived free light chains (FLCs) by only 1 day after immunization. Unlike conventional B-1a (cB-1a) cell-produced IgM natural Ab, IgM Ab produced by sB-1a cells has high Ag affinity owing to immunoglobulin V-region mutations induced by activation-induced cytidine deaminase (AID). The dominant cB-1a cells are increased in immunized AID-deficient mice but do not mediate initiation, CS, or pneumonia resistance because natural Ab has relatively low Ag affinity because of unmutated germ-line V regions. In CS and DTH, sB-1a IgM Ag affinity is sufficiently high to mediate complement activation for generation of C5a that, together with vasoactive mediators such as TNF-α released by FLC-sensitized mast cells, activate local endothelium for extravascular recruitment of effector T cells. We conclude by discussing the possibility of functional sB-1 cells in humans.
authors.affiliation: Department of Internal Medicine, Section of Allergy and Clinical Immunology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Phillip W
authors.initials: PW
authors.lastname: Askenase
authors.affiliation: Department of Immunology, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Bryniarski
authors.affiliation: Department of Internal Medicine, Section of Allergy and Clinical Immunology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Vipin
authors.initials: V
authors.lastname: Paliwal
authors.affiliation: Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Redegeld
authors.affiliation: Department of Internal Medicine, Section of Allergy and Clinical Immunology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Thomas
authors.initials: T
authors.lastname: Groot Kormelink
authors.affiliation: Department of Internal Medicine, Section of Allergy and Clinical Immunology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Steven
authors.initials: S
authors.lastname: Kerfoot
authors.affiliation: Department of Internal Medicine, Section of Allergy and Clinical Immunology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hutchinson
authors.affiliation: Department of Internal Medicine, Section of Allergy and Clinical Immunology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Henk
authors.initials: H
authors.lastname: van Loveren
authors.affiliation: Department of Internal Medicine, Section of Allergy and Clinical Immunology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Regis
authors.initials: R
authors.lastname: Campos
authors.affiliation: Department of Internal Medicine, Section of Allergy and Clinical Immunology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Itakura
authors.affiliation: Department of Medical Biology, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Majewska-Szczepanik
authors.affiliation: Department of Infection Control and Laboratory Medicine, Fukushima Medical University, Fukushima, Japan.
authors.forename: Natsuo
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Department of Immunology, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Katarzyn
authors.initials: K
authors.lastname: Nazimek
authors.affiliation: Department of Medical Biology, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Marian
authors.initials: M
authors.lastname: Szczepanik
authors.affiliation: Department of Immunology, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Wold
authors.initials: W
authors.lastname: Ptak
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D003564:Cytidine Deaminase / Q000172:deficiency / Q000276:immunology*; D003877:Dermatitis, Contact / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity; D007114:Immunization; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D051379:Mice; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000517:prevention & control; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase
keywords: AID; B cell; CS; delayed-type hypersensitivity; DTH; activation-induced deaminase; contact sensitivity; free antibody light chains; FLC; interleukin 4; pneumococcal pneumonia