Selective Regulation of Mature IgG1 Transcription by CD86 and β2-Adrenergic Receptor Stimulation
- 15 May 2003
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 170 (10), 5143-5151
- https://doi.org/10.4049/jimmunol.170.10.5143
Abstract
Stimulation of CD86 and the beta(2)-adrenergic receptor (beta(2)AR) on a B cell, either alone or together, is known to increase the level of IgG1 protein produced by a CD40 ligand/IL-4-activated B cell. It is also known that the mechanism by which CD40 and IL-4R stimulation on a B cell increases the level of IgG1 protein is by increasing germline gamma 1 transcription, IgG1 class switching, and mature IgG1 transcription, while the molecular mechanism responsible for mediating the CD86- and beta(2)AR-induced effect remains unknown. In the present study using real-time PCR we show that the level of mature IgG1 transcription increases in CD40 ligand/IL-4-activated B cells following stimulation of either CD86 and/or beta(2)AR, and that this increase reflects the increase in IgG1 protein. Furthermore, we show that the CD86- and/or beta(2)AR-induced increase in mature IgG1 transcript is due to an increase in the rate of mature IgG1 transcription, as determined by nuclear run-on analysis. This effect is additive when both receptors are stimulated and is lost when B cells from CD86- and beta(2)AR-deficient mice are used. In contrast, the level of germline gamma 1 transcription, the stability of mature IgG1 transcript, the number of IgG1-positive B cells, and the number of IgG1-secreting B cells did not change. These results provide the first evidence that CD86 and/or beta(2)AR stimulation on a CD40 ligand/IL-4-activated B cell increases the level of IgG1 protein produced per cell by increasing the rate of mature IgG1 transcription.This publication has 59 references indexed in Scilit:
- The B7–CD28 superfamilyNature Reviews Immunology, 2002
- B7-1 and B7-2 Have Overlapping, Critical Roles in Immunoglobulin Class Switching and Germinal Center FormationImmunity, 1997
- B7–2 (CD86) is essential for the development of IL-4-producing T cellsInternational Immunology, 1996
- Induction of costimulatory molecules B7-1 and B7-2 in murine B cells: The CBAN mouse reveals a role for Bruton's tyrosine kinase in CD40-mediated B7 inductionMolecular Immunology, 1996
- Mechanism of enhanced antigen presentation by B cells activated with anti‐μ plus interferon‐γ: Role of B7‐2 in the activation of naive and memory CD4+ T cellsEuropean Journal of Immunology, 1995
- Studies on the interdependence of gp39 and B7 expression and function during antigen‐specific immune responsesEuropean Journal of Immunology, 1995
- In vitro induction of T cell anergy by blocking B7 and early T cell costimulatory molecule ETC-1/B7-2Immunity, 1994
- IL-4-induced expression of germline γ1 transcripts in B cells following cognate interactions with T helper cellsInternational Immunology, 1992
- Induction of germ‐line immunoglobulin heavy chain transcripts by mitogens and interleukins prior to switch recombinationEuropean Journal of Immunology, 1990
- A High Production Rate of Translatable IgG mRNA Accounts for the Amplified Synthesis of IgG in Myeloma CellsJBIC Journal of Biological Inorganic Chemistry, 1980