Induced expression of murine gamma2a by CD40 ligation independently of IFN-gamma.
IgG2a, with gamma2a H chains, is important for protection against viruses and other intracellular pathogens. Although a large portion of IgG2a expression is dependent upon IFN-gamma, some germline transcription and switch recombination to the murine gamma2a H chain gene expression are independent of IFN-gamma. We found that agonistic anti-CD40 Abs injected into IFN-gamma-deficient mice induce a > 200-fold increase in the amount of serum Ig2a, while other Ig isotypes are increased by 16-fold or less. In vitro, ligation of CD40 on B cells, without the addition of other B cell activators or cytokines, results in germline transcription and switch recombination that are largely restricted to the gamma2a gene. These results suggest that some immune responses to infectious agents can result in large amounts of IgG2a expression through ligation of CD40, without the expression of IFN-gamma by Th1 or other cells.
Collins
John T
JT
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109-0620, USA.
Shi
Jian
J
Burrell
Bryna E
BE
Bishop
D Keith
DK
Dunnick
Wesley A
WA
D000818:Animals; D019013:CD40 Antigens / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D015321:Gene Rearrangement; D018095:Germ-Line Mutation; D007109:Immunity / Q000235:genetics; D017578:Immunoglobulin Class Switching; D007132:Immunoglobulin Isotypes / Q000235:genetics; D007142:Immunoglobulin gamma-Chains / Q000235:genetics*; D007239:Infections / Q000276:immunology; D007371:Interferon-gamma / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D014158:Transcription, Genetic
D019013:CD40 Antigens; D007132:Immunoglobulin Isotypes; D007142:Immunoglobulin gamma-Chains; D007371:Interferon-gamma