Receptor-mediated elimination of phosphocholine-specific B cells in x-linked immune-deficient mice.
The combined expression of the M167 mu/kappa anstiphosphocholine (PC) transgenes with the x-linked immunodeficiency gene, xid, results in an almost total failure to develop B cells in the peripheral lymphoid organs of such mice. Although there is no significant difference between the normal transgene positive (TG+) female offspring and the immunodeficient TG+ xid males with respect to the number of B220+ pre-B cells and IgM+B220+B cells that develop in their bone marrow, the hemizygous xid males have 85% fewer B cells in their spleens than the phenotypically normal heterozygous F1 females. In xid M167-mu-transgenic mice, PC-specific B cells also fail to develop in the spleen; however, numerous B cells bearing the mua+VH1(+)-transgene product associated with endogenous kappa L chains that do not give rise PC-specific antibodies are present. In the phenotypically normal TG+ (B6.CBA/N x mu 243-4)F1 female mice, PC-specific B cells represent almost 10% of the total B cell population, and these B cells express an M167-Id that has been produced by association of the VH1 transgene product with an endogenous V kappa 24L chain. B cells expressing the normally dominant T15-Id are not detectable in the spleens of these M167 mu-transgenic mice. Furthermore, M167-Id+ B cells are present at a fivefold lower level in the bone marrow of mu-TG+ normal mice than in their spleens. These data suggest that the PC-specific B cells that develop in TG+ xid mice are either clonally deleted via some "IgR-directed" mechanism or they fail to receive the appropriate signals to exit the bone marrow or to enter the peripheral lymphoid tissues. This hypothesis is supported by the finding that TNP-specific B cells develop normally and do not undergo clonal deletion in xid mice carrying the Sp6 mu/kappa anti-TNP transgenes.
Kenny
J J
JJ
Program Resources Inc./DynCorp. NCI-FCRDC, Frederick, MD 21702-1201.
Stall
A M
AM
Sieckmann
D G
DG
Lamers
M C
MC
Finkelman
F D
FD
Finch
L
L
Longo
D L
DL
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001854:Bone Marrow Cells; D005434:Flow Cytometry; D008040:Genetic Linkage; D007108:Immune Tolerance / Q000235:genetics*; D007075:Immunoglobulin M / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D010767:Phosphorylcholine / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D014960:X Chromosome
D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains; D010767:Phosphorylcholine