Apoptosis induced by crosslinking of CD4 on activated human B cells.
Using immunofluorescence, RT-PCR, and Western blotting, we have demonstrated the ability of human B cells to express CD4. In each of the 10 lymphoblastoid cell lines (LCL) tested there was variable, but definite, proportion of CD4-positive B cells. Expression of CD4 was related to the cell cycle; CD4 was expressed in the G1 phase and continued at later phases of the cell cycle. CD4 was in part internalized and degraded by the LCL B cells. Surface CD4 was associated to lck and its crosslinking resulted in tyrosine phosphorylation. Additional experiments conducted on freshly prepared tonsillar B cells demonstrated that CD4 was expressed by large activated B cells, but not by small resting B cells. However, not all the activated tonsillar B cells had surface CD4 since germinal center cells were CD4-negative. Crosslinking of CD4 on LCL or on tonsillar activated B cells resulted in apoptosis in vitro, a finding that indicates the capacity of CD4 to deliver functional signals to B cells and to play a regulatory function in their physiology. Exposure of CD4 expressing B cells to gp120 under conditions that resulted in CD4 crosslinking also caused apoptosis suggesting some implications for the pathophysiology of AIDS.
Cutrona
G
G
Istituto Nazionale per la Ricerca sul Cancro, IST-Servizio di Immunologia Clinica, Genoa, 16132, Italy.
Leanza
N
N
Ulivi
M
M
Majolini
M B
MB
Taborelli
G
G
Zupo
S
S
Baldari
C T
CT
Roncella
S
S
Ferrarini
M
M
D017209:Apoptosis; D001402:B-Lymphocytes / Q000502:physiology*; D015704:CD4 Antigens / Q000032:analysis / Q000502:physiology*; D002453:Cell Cycle; D002460:Cell Line; D015699:HIV Envelope Protein gp120 / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000032:analysis
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)