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Departments of
*
Microbiology and Immunology, and
Cell Biology, Neurobiology and Anatomy, Loyola University Medical Center, Maywood, IL 60153;
Department of Microbiology, University of Texas Health Science Center, San Antonio, TX 78284;
§
Department of Medicine and Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305; and
¶
Department of Pathology, Brigham and Women’s Hospital, Boston MA 02115
Our findings using B cells from either wild-type, CD86-deficient, or ß2-adrenergic receptor (ß2AR)-deficient mice suggest three mechanisms by which the level of IgG1 and IgE production can be increased on a per cell basis. Trinitrophenyl-specific B cells enriched from unimmunized mouse spleens were pre-exposed to Ag and/or the ß2AR ligand terbutaline for 24 h before being activated by either a ß2AR-negative Th2 cell clone or CD40 ligand/Sf9 cells and IL-4 in the presence or absence of an anti-CD86 Ab. Data suggest that the first mechanism involves a B cell receptor (BCR)-dependent up-regulation of CD86 expression that, when CD86 is stimulated, increases the amount of IgG1 and IgE produced in comparison to unstimulated cells. The second mechanism involves a BCR- and ß2AR-dependent up-regulation of CD86 to a level higher than that induced by stimulation of either receptor alone that, when CD86 is stimulated, further increases the amount of IgG1 and IgE produced. The third mechanism is BCR-independent and involves a ß2AR-dependent increase in the ability of a B cell to respond to IL-4. Flow cytometric and limiting dilution analyses suggest that the increase in IgG1 and IgE occurs independently from the isotype switching event. These findings suggest that the BCR, the ß2AR, and CD86 are involved in regulating IL-4-dependent IgG1 and IgE production.
This article has been cited by other articles:
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G. Pongratz, J. W. McAlees, D. H. Conrad, R. S. Erbe, K. M. Haas, and V. M. Sanders The Level of IgE Produced by a B Cell Is Regulated by Norepinephrine in a p38 MAPK- and CD23-Dependent Manner. J. Immunol., September 1, 2006; 177(5): 2926 - 2938. [Abstract] [Full Text] [PDF]
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 N. W. Kin and V. M. Sanders It takes nerve to tell T and B cells what to do J. Leukoc. Biol., June 1, 2006; 79(6): 1093 - 1104. [Abstract] [Full Text] [PDF]
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N. W. Kin and V. M. Sanders CD86 Stimulation on a B Cell Activates the Phosphatidylinositol 3-Kinase/Akt and Phospholipase C{gamma}2/Protein Kinase C{alpha}beta Signaling Pathways. J. Immunol., June 1, 2006; 176(11): 6727 - 6735. [Abstract] [Full Text] [PDF]
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T. Jinquan, H. H. Jacobi, C. Jing, A. Millner, E. Sten, L. Hviid, L. Anting, L. P. Ryder, C. Glue, P. S. Skov, et al. CCR3 Expression Induced by IL-2 and IL-4 Functioning as a Death Receptor for B Cells J. Immunol., August 15, 2003; 171(4): 1722 - 1731. [Abstract] [Full Text] [PDF]
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 C.-M. Hogerkorp, S. Bilke, T. Breslin, S. Ingvarsson, and C. A. K. Borrebaeck CD44-stimulated human B cells express transcripts specifically involved in immunomodulation and inflammation as analyzed by DNA microarrays Blood, March 15, 2003; 101(6): 2307 - 2313. [Abstract] [Full Text] [PDF]
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 L. G. Thebeau and L. A. Morrison Mechanism of Reduced T-Cell Effector Functions and Class-Switched Antibody Responses to Herpes Simplex Virus Type 2 in the Absence of B7 Costimulation J. Virol., February 15, 2003; 77(4): 2426 - 2435. [Abstract] [Full Text] [PDF]
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 H. K. Takahashi, T. Morichika, H. Iwagaki, T. Yoshino, R. Tamura, S. Saito, S. Mori, T. Akagi, N. Tanaka, and M. Nishibori Effect of {beta}2-Adrenergic Receptor Stimulation on Interleukin-18-Induced Intercellular Adhesion Molecule-1 Expression and Cytokine Production J. Pharmacol. Exp. Ther., February 1, 2003; 304(2): 634 - 642. [Abstract] [Full Text] [PDF]
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J. M. Lumsden, J. A. Williams, and R. J. Hodes Differential Requirements for Expression of CD80/86 and CD40 on B Cells for T-Dependent Antibody Responses In Vivo J. Immunol., January 15, 2003; 170(2): 781 - 787. [Abstract] [Full Text] [PDF]
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 C. S. Schmidt, J. Liu, T. Zhang, H. Y. Song, G. Sandusky, K. Mintze, R. J. Benschop, A. Glasebrook, D. D. Yang, and S. Na Enhanced B Cell Expansion, Survival, and Humoral Responses by Targeting Death Receptor 6 J. Exp. Med., January 6, 2003; 197(1): 51 - 62. [Abstract] [Full Text] [PDF]
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 J.-H. Shim, H.-K. Lee, E.-J. Chang, W.-J. Chae, J.-H. Han, D.-J. Han, T. Morio, J.-J. Yang, A. Bothwell, and S.-K. Lee Immunosuppressive effects of tautomycetin in vivo and in vitro via T cell-specific apoptosis induction PNAS, August 6, 2002; 99(16): 10617 - 10622. [Abstract] [Full Text] [PDF]
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 S. Ek, C.-M. Hogerkorp, M. Dictor, M. Ehinger, and C. A. K. Borrebaeck Mantle Cell Lymphomas Express a Distinct Genetic Signature Affecting Lymphocyte Trafficking and Growth Regulation as Compared with Subpopulations of Normal Human B Cells Cancer Res., August 1, 2002; 62(15): 4398 - 4405. [Abstract] [Full Text] [PDF]
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A. P. Kohm, A. Mozaffarian, and V. M. Sanders B Cell Receptor- and {beta}2-Adrenergic Receptor-Induced Regulation of B7-2 (CD86) Expression in B Cells J. Immunol., June 15, 2002; 168(12): 6314 - 6322. [Abstract] [Full Text] [PDF]
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 A. P. Kohm and V. M. Sanders Norepinephrine and beta 2-Adrenergic Receptor Stimulation Regulate CD4+ T and B Lymphocyte Function in Vitro and in Vivo Pharmacol. Rev., December 1, 2001; 53(4): 487 - 525. [Abstract] [Full Text] [PDF]
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