Burst-enhancing role of the IgG membrane tail as a molecular determinant of memory.
The basis of immune memory leading to heightened secondary antibody responses is a longstanding unanswered issue. Here we show that a single irreversible molecular change in the B cell antigen receptor, which is brought about by immunoglobulin M (IgM) to IgG isotype switching, is sufficient to greatly increase the extrafollicular proliferative burst of antigen-specific B cells. The unique membrane-spanning regions of IgG do not alter the T cell-dependent activation and proliferation of antigen-specific B cells in vivo, but markedly increase the number of progeny cells and plasmablasts that accumulate. These results establish a key molecular determinant of immunological memory and define an unexpected cellular basis by which it enhances the magnitude of secondary antibody responses.
Martin
Stephen W
SW
ACRF Genetics Laboratory, Medical Genome Centre, John Curtin School of Medical Research, Australian National University, PO Box 334, Mills Road, Canberra 2601, Australia.
Goodnow
Christopher C
CC
D000595:Amino Acid Sequence; D000818:Animals; D000915:Antibody Affinity; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D007117:Immunization, Secondary; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000096:biosynthesis; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009113:Muramidase / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis*; D013154:Spleen / Q000166:cytology / Q000276:immunology
D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D009113:Muramidase