Human appendix B cells naturally express receptors for and respond to interleukin 6 with selective IgA1 and IgA2 synthesis.
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.
Fujihashi
K
K
Department of Oral Biology, University of Alabama at Birmingham 35294.
McGhee
J R
JR
Lue
C
C
Beagley
K W
KW
Taga
T
T
Hirano
T
T
Kishimoto
T
T
Mestecky
J
J
Kiyono
H
H
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
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