bcl-2 alters the antigen-driven selection of B cells in mukappa but not in mu-only Xid transgenic mice.
A point mutation in the pleckstrin homology domain of the mouse Bruton's tyrosine kinase (btk) gene results in an X-linked immune defect, Xid, characterized by immunologic unresponsiveness to polymeric carbohydrate Ags. In Xid mice, B cells specific for phosphocholine (PC) do not develop in peripheral lymphoid tissues because they either fail to be positively selected from the marrow or they are clonally deleted via an Ag-driven, receptor-mediated process. Overexpression of the bcl-2 gene allows PC-specific B cells to survive and mature in Xid mukappa anti-PC transgenic mice, but PC-specific B cells are not rescued by bcl-2 in Xid mu-only transgenic mice. The failure of bcl-2 to rescue PC-specific B cells, in mu-only transgenic mice suggests that either it does not correct the btk defect in the Ag-driven selection process that occurs in pre-B cells and/or in very immature B cells or that a btk-dependent proliferative phase is required for the selection and amplification of the PC-specific B cells in mu-only transgenic mice. The rescue of PC-specific B cells in mukappa transgenic mice indicates that bcl-2 can alter receptor-mediated B cell selection at late stages in B cell development. The rescued PC-specific B cells in Xid male mice do not exhibit an altered proliferation profile in response to B cell-stimulating agents compared with B cells from unmanipulated Xid mice; thus, they fail to respond to soluble anti-mu, or PC-dextran, but they proliferate in response to PC, anti-mu, or anti-id conjugated to Sepharose.
Kenny
J J
JJ
Biologic Carcinogenesis Development Program/Science Applications International Corporation-Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702, USA.
Fischer
R T
RT
Lustig
A
A
Dintzis
H
H
Katsumata
M
M
Reed
J C
JC
Longo
D L
DL
D000818:Animals; D000955:Antigens, T-Independent / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D001483:Base Sequence; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D017637:Clonal Deletion; D005260:Female; D005434:Flow Cytometry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010641:Phenotype; D010767:Phosphorylcholine / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D017455:Receptors, IgE / Q000032:analysis; D013154:Spleen / Q000166:cytology
D000955:Antigens, T-Independent; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017455:Receptors, IgE; D010767:Phosphorylcholine