Rescue of self-reactive B cells by provision of T cell help in vivo. 1998

M C Cook, and A Basten, and B Fazekas de St Groth
Centenary Institute of Cancer Medicine and Cell Biology, Newtown, NSW, Australia.

We have previously demonstrated that antigen-specific T cell help can rescue mature Ig transgenic (Tg) hen egg lysozyme (HEL)-specific B cells from tolerance induction upon transfer into soluble HEL-expressing Tg hosts. Here we extend these findings by showing that T cell help could also rescue both immature and mature self-reactive B cells from rapid deletion in response to high-avidity membrane-bound HEL. Moreover, although short-lived anergic peripheral B cells that had matured in the presence of soluble self antigen could not be rescued by provision of T cell help, a proportion of immature anergic IgM+ IgD- CD23- B cells from the bone marrow of the same donors survived and proliferated when given help following transfer to a soluble or membrane HEL-expressing host. In other words, T cell help must be available relatively soon after the antigen signal to prevent induction of tolerance. Consistent with this interpretation, the stronger stimulus provided by membrane-bound antigen, which deletes immature B cells before they leave the bone marrow, did not afford an opportunity for T cell help to rescue tolerant immature bone marrow-derived B cells upon transfer in vivo. Nevertheless, these B cells were capable of responding to T cell help in vitro, which speaks against an immutable susceptibility of immature B cells to tolerance induction. Taken together, these data indicate that the strength of the antigen signal and availability of T cell help are the primary determinants of the fate of both immature and mature B cells, consistent with the model proposed by Bretscher and Cohn more than 25 years ago.

UI MeSH Term Description Entries
D008211 Lymphocyte Cooperation T-cell enhancement of the B-cell response to thymic-dependent antigens. Cooperation, Lymphocyte,Cooperations, Lymphocyte,Lymphocyte Cooperations
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D009113 Muramidase A basic enzyme that is present in saliva, tears, egg white, and many animal fluids. It functions as an antibacterial agent. The enzyme catalyzes the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in peptidoglycan and between N-acetyl-D-glucosamine residues in chitodextrin. EC 3.2.1.17. Lysozyme,Leftose,N-Acetylmuramide Glycanhydrolase,Glycanhydrolase, N-Acetylmuramide,N Acetylmuramide Glycanhydrolase
D011948 Receptors, Antigen, T-Cell Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (CD3 COMPLEX). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains. Antigen Receptors, T-Cell,T-Cell Receptors,Receptors, T-Cell Antigen,T-Cell Antigen Receptor,T-Cell Receptor,Antigen Receptor, T-Cell,Antigen Receptors, T Cell,Receptor, T-Cell,Receptor, T-Cell Antigen,Receptors, T Cell Antigen,Receptors, T-Cell,T Cell Antigen Receptor,T Cell Receptor,T Cell Receptors,T-Cell Antigen Receptors
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002645 Chickens Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA. Gallus gallus,Gallus domesticus,Gallus gallus domesticus,Chicken
D006183 H-2 Antigens The major group of transplantation antigens in the mouse. H2 Antigens,Antigens, H-2,Antigens, H2,H 2 Antigens
D006377 T-Lymphocytes, Helper-Inducer Subpopulation of CD4+ lymphocytes that cooperate with other lymphocytes (either T or B) to initiate a variety of immune functions. For example, helper-inducer T-cells cooperate with B-cells to produce antibodies to thymus-dependent antigens and with other subpopulations of T-cells to initiate a variety of cell-mediated immune functions. Helper Cell,Helper Cells,Helper T Cell,Helper-Inducer T-Lymphocytes,Inducer Cell,Inducer Cells,T-Cells, Helper-Inducer,T-Lymphocytes, Helper,T-Lymphocytes, Inducer,Helper T-Cells,Cell, Helper T,Cells, Helper T,Helper Inducer T Lymphocytes,Helper T Cells,Helper T-Cell,Helper T-Lymphocyte,Helper T-Lymphocytes,Helper-Inducer T-Cell,Helper-Inducer T-Cells,Helper-Inducer T-Lymphocyte,Inducer T-Lymphocyte,Inducer T-Lymphocytes,T Cell, Helper,T Cells, Helper,T Cells, Helper Inducer,T Lymphocytes, Helper,T Lymphocytes, Helper Inducer,T Lymphocytes, Inducer,T-Cell, Helper,T-Cell, Helper-Inducer,T-Cells, Helper,T-Lymphocyte, Helper,T-Lymphocyte, Helper-Inducer,T-Lymphocyte, Inducer
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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