Isolation of cDNAs encoding T-BAM, a surface glycoprotein on CD4+ T cells mediating contact-dependent helper function for B cells: identity with the CD40-ligand.
"T-cell B-cell Activating Molecule" (T-BAM) is an activation-induced surface protein on CD4+ T cells that mediates a contact-dependent signal for B cell differentiation and immunoglobulin (Ig) secretion. The T-BAM protein on a helper clone of Jurkat (D1.1) was affinity purified using the anti-T-BAM mAb, 5c8. The NH2-terminal amino acid sequence of purified T-BAM was determined and found to be highly homologous to the predicted NH2-terminal sequence of a T cell ligand to the B cell CD40 molecule (CD40-L). From a D1.1 cDNA library, a clone was isolated that encodes CD40-L by sequence and drives expression of T-BAM protein on transfected cells, demonstrating that the T-BAM and CD40-L genes and proteins are identical. Moreover, transfection of T-BAM was shown to confer to non-lymphoid cells, the ability to induce B cells to upregulate the expression of surface CD23 molecules. In previous studies we showed that T-BAM was expressed predominantly on activated CD4+ and on few if any CD8+ cells. Although the current work confirms that T-BAM is largely restricted to activated CD4+ T cells, we now provide definitive evidence that T-BAM can be expressed by a small population of CD8+ T cells after activation. Importantly, a subset of CD8+ T cells do not express T-BAM after activation and this T-BAM- phenotype is maintained on certain CD8+ T cell clones. Taken together, these data unify the biology and structure of T-BAM and CD40-L and this synthesis has implications for understanding the T cell regulation of the humoral immune response.
Covey
L R
LR
Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY 10032.
Cleary
A M
AM
Yellin
M J
MJ
Ware
R
R
Sullivan
G
G
Belko
J
J
Parker
M
M
Rothman
P
P
Chess
L
L
Lederman
S
S
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D019013:CD40 Antigens; D023201:CD40 Ligand; D016827:CD8 Antigens / Q000276:immunology; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D008969:Molecular Sequence Data; D017455:Receptors, IgE / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis; D017421:Sequence Analysis; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000737:chemistry / Q000276:immunology*; D015854:Up-Regulation
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D016827:CD8 Antigens; D018076:DNA, Complementary; D008024:Ligands; D008562:Membrane Glycoproteins; D017455:Receptors, IgE; D011994:Recombinant Proteins; D023201:CD40 Ligand