title: Human appendix B cells naturally express receptors for and respond to interleukin 6 with selective IgA1 and IgA2 synthesis.
abstract: Past studies have shown that freshly isolated human B cells from peripheral blood and tonsils do not express IL-6 receptors (IL-6R); however, mitogen or antigen activation of these B cells induces IL-6R and responsiveness to IL-6. In this study, we have shown that a high proportion of B cells enzymatically dissociated from human appendix, a gut-associated lymphoreticular tissue (GALT), expresses the IL-6R, and that recombinant human IL-6 induces significant increases in the number of Ig-producing cells. The recombinant human IL-6-induced increase in Ig-producing cells is restricted to the IgA isotype. Further, IgA2 is the major subclass; however, significant numbers of IgA1 producing cells are also seen. In contrast, human tonsillar and peripheral blood B cells express low levels of IL-6R, and exogenous IL-6 does not increase numbers of Ig-producing cells. When PBMC or tonsillar cells are stimulated with PWM, the former display an equal distribution of IgA1 and IgA2 secreting cells, while tonsillar B cells are mainly of the IgA1 subclass. The distribution of surface Ig-positive (sIg+) B cells in the appendix B cell population is sIgA+ greater than sIgG+ greater than sIgM+, and the sIgA+ B cells express higher levels of IL-6R when compared with sIgG+ or sIgM+ B cells. These studies show that human appendix contains B cell subsets that constitutively express IL-6R, and that a high proportion of these cells are committed to the IgA isotype. Furthermore, higher numbers of IL-6 responsive IgA2 B cells are present in the human appendix as compared to tonsils or PBMC.
authors.affiliation: Department of Oral Biology, University of Alabama at Birmingham 35294.
authors.forename: K
authors.initials: K
authors.lastname: Fujihashi
authors.forename: J R
authors.initials: JR
authors.lastname: McGhee
authors.forename: C
authors.initials: C
authors.lastname: Lue
authors.forename: K W
authors.initials: KW
authors.lastname: Beagley
authors.forename: T
authors.initials: T
authors.lastname: Taga
authors.forename: T
authors.initials: T
authors.lastname: Hirano
authors.forename: T
authors.initials: T
authors.lastname: Kishimoto
authors.forename: J
authors.initials: J
authors.lastname: Mestecky
authors.forename: H
authors.initials: H
authors.lastname: Kiyono
mesh_terms: D001065:Appendix / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis* / Q000145:classification; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000494:pharmacology*; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000032:analysis*; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015850:Interleukin-6; D011947:Receptors, Antigen, B-Cell; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins