B cells from M167 mu kappa transgenic mice fail to proliferate after stimulation with soluble anti-Ig antibodies. A model for antigen-induced B cell anergy.
The transgenic (TG) mouse strain 207-4, carries mu a + kappa transgenes ligated to the anti-phosphocholine (PC) VH1 and V kappa 24 V region genes from the MOPC-167 myeloma. Although B cells from mice carrying these transgenes respond both in vivo and in vitro to thymus-dependent Ags, they failed to proliferate in response to soluble goat anti-mu Ab or other soluble anti-Ig reagents. On the other hand, B cells from the Sp6 mu kappa anti-trinitrophenyl TG mouse line proliferated normally after stimulation with soluble anti-mu. However, the 207-4 anti-PC transgene positive (TG+) splenic B cells proliferated when stimulated with anti-mu, anti-idiotype, anti-allotype, or PC-conjugated to Sepharose beads. TG+ B cells were also induced to proliferate when stimulated with anti-Lyb-2; thus, their defect may be restricted to signaling through sigM. The lack of response to soluble anti-mu could not be reversed by addition of IL-4, by removal of T cells, by addition of anti-FcR Ab, or by stimulation with F(ab')2 anti-mu. Thus, the failure to proliferate was not caused by active T cell suppression or FcR-mediated inhibition. In mixed cultures of TG+ and transgene negative (TG-) spleen cells, the TG- cells were able to proliferate normally to soluble anti-mu, indicating that suppressive factors were not involved in the unresponsiveness of the TG+ anti-PC-specific B cells. These studies suggest that B cells in the 207-4 anti-PC TG mice exhibit a defect in activation through their sIgM receptors, and this unresponsiveness may reflect a form of Ag-induced tolerance.
Sieckmann
D G
DG
Infectious Diseases Department, Naval Medical Research Institute, Bethesda, MD 20889-5607.
Holmes
K
K
Hornbeck
P
P
Martin
E
E
Guelde
G
G
Bondada
S
S
Longo
D L
DL
Kenny
J J
JJ
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000950:Antigens, Ly / Q000032:analysis / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D007108:Immune Tolerance; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology*; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation; D016177:Macrophage-1 Antigen / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011961:Receptors, Fc / Q000502:physiology
D000888:Antibodies, Anti-Idiotypic; D000950:Antigens, Ly; D007075:Immunoglobulin M; D016177:Macrophage-1 Antigen; D011961:Receptors, Fc; D015847:Interleukin-4