Signal transduction through mu kappa B-cell receptors expressed on pre-B cells is different from that through B-cell receptors on mature B cells.
We introduced kappa light chain genes into pre-B cells to increase the surface mu HC expression, and established transfectants expressing mature type of B-cell receptors (BCR) on pre-B-cell surfaces. Since the cytoplasmic conformations of the reconstituted BCR and intrinsic pre-B-cell receptor (pre-BCR) are identical, they would be connected with the identical signal transduction pathways in pre-B cells. By using the transfectants, we revealed that the reconstituted BCR on pre-B cells was functionally equivalent to BCR on mature B cells in terms of the induction of intracellular Ca++ mobilization. However, we found that the signal-transduction pathways through BCR on pre-B cells were quantitatively different from those mature B cells in two ways. First, cross-linkage of the reconstituted BCR on pre-B cells induced preferential tyrosine phosphorylation of p120 and p100, which was not observed when BCR on mature B cells was cross-linked. Second, BCR in pre-B cells was physically associated with a larger amount of phosphatidylinositol-3 kinase (PI-3K) than BCR in mature B cells in spite of the fact that both pre-B and B cells expressed a similar amount of PI-3K in cytoplasm. Signals through pre-BCR and BCR are known to cause distinct biological effects in B-cell development. The biochemical features in the downstream of reconstituted BCR on pre-B cells, which we revealed in this study, will be of help in understanding the mechanism of functional differences between pre-BCR and BCR.
Nakamura
T
T
Department of Infectious Diseases and Applied Immunology, University of Tokyo, Japan.
Koyama
M
M
Yoneyama
A
A
Higashihara
M
M
Kawakami
T
T
Yamamura
H
H
Sada
K
K
Okumura
K
K
Kurokawa
K
K
D001402:B-Lymphocytes / Q000276:immunology*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000276:immunology; D007148:Immunoglobulin mu-Chains / Q000276:immunology; D010766:Phosphorylation; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D014162:Transfection; D014443:Tyrosine
D007145:Immunoglobulin kappa-Chains; D007148:Immunoglobulin mu-Chains; D011947:Receptors, Antigen, B-Cell; D014443:Tyrosine; D002118:Calcium