TY - JOUR
T1 - B cells from M167 μκ transgenic mice fail to proliferate after stimulation with soluble anti-lg antibodies
T2 - A model for antigen-induced B cell anergy
AU - Sieckmann, D. G.
AU - Holmes, K.
AU - Hornbeck, P.
AU - Martin, E.
AU - Guelde, G.
AU - Bondada, S.
AU - Longo, D. L.
AU - Kenny, J. J.
PY - 1994/5/15
Y1 - 1994/5/15
N2 - The transgenic (TG) mouse strain 207-4, carries μa + κ transgenes ligated to the anti-phosphocholine (PC) VH1 and Vκ24 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-μ Ab or other soluble anti-lg reagents. On the other hand, B cells from the Sp6 μκ anti-trinitrophenyl TG mouse line proliferated normally after stimulation with soluble anti-μ. However, the 207-4 anti-PC transgene positive (TG+) splenic B cells proliferated when stimulated with anti-μ, 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 slgM. The lack of response to soluble anti-μ 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-μ. 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-μ, 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 slgM receptors, and this unresponsiveness may reflect a form of Ag-induced tolerance.
AB - The transgenic (TG) mouse strain 207-4, carries μa + κ transgenes ligated to the anti-phosphocholine (PC) VH1 and Vκ24 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-μ Ab or other soluble anti-lg reagents. On the other hand, B cells from the Sp6 μκ anti-trinitrophenyl TG mouse line proliferated normally after stimulation with soluble anti-μ. However, the 207-4 anti-PC transgene positive (TG+) splenic B cells proliferated when stimulated with anti-μ, 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 slgM. The lack of response to soluble anti-μ 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-μ. 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-μ, 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 slgM receptors, and this unresponsiveness may reflect a form of Ag-induced tolerance.
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M3 - Article
C2 - 8176209
AN - SCOPUS:0028231661
SN - 0022-1767
VL - 152
SP - 4873
EP - 4883
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -