© The Rockefeller University Press, 0022-1007/2000/3/1031/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 6, March 20, 2000 1031-1044
Gene Dose–dependent Maturation and Receptor Editing of B Cells Expressing Immunoglobulin (Ig)G1 or IgM/IgG1 Tail Antigen Receptors
Sarah L. Poguea and
Christopher C. Goodnowb
a Department of Microbiology and Immunology and Howard Hughes Medical Institute, Stanford University, Palo Alto, California 94305
b Medical Genome Centre, Australian Cancer Research Foundation Genetics Laboratory, John Curtin School of Medical Research, Australian National University Canberra, Canberra ACT 2601, Australia
Correspondence to:
Christopher C. Goodnow, John Curtin School of Medical Research, Mills Rd., Australian National University, P.O. Box 334, Canberra ACT 2601, Australia. Tel:61-2-6249-3621 Fax:61-2-6279-8512 E-mail:Chris.Goodnow{at}anu.edu.au.
Released online: 20 March 2000
Conserved differences between the transmembrane and cytoplasmic domains of membrane immunoglobulin (Ig)M and IgG may alter the function of antigen receptors on naive versus memory B cells. Here, we compare the ability of these domains to signal B cell allelic exclusion and maturation in transgenic mice. A lysozyme-binding antibody was expressed in parallel sets of mice as IgM, IgG1, or a chimeric receptor with IgM extracellular domains and transmembrane/cytoplasmic domains of IgG1. Like IgM, the IgG1 or chimeric IgM/G receptors triggered heavy chain allelic exclusion and supported development of mature CD21+ B cells. Many of the IgG or IgM/G B cells became CD21high and downregulated their IgG and IgM/G receptors spontaneously, resembling memory B cells and B cells with mutations that exaggerate B cell antigen receptor signaling. Unlike IgM-transgenic mice, "edited" B cells that carry non–hen egg lysozyme binding receptors preferentially accumulated in IgG and IgM/G mice. This was most extreme in lines with the highest transgene copy number and diminished in variant offspring with fewer copies. The sensitivity of B cell maturation to transgene copy number conferred by the IgG transmembrane and cytoplasmic domains may explain the diverse phenotypes found in other IgG-transgenic mouse strains and may reflect exaggerated signaling.
Key Words:
B lymphocyte, development, isotype switch, allelic exclusion, transgene
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