Adhesion through the LFA-1 (CD11a/CD18)-ICAM-1 (CD54) and the VLA-4 (CD49d)-VCAM-1 (CD106) pathways prevents apoptosis of germinal center B cells.
In the germinal center (GC), B cells are either selected to become memory cells or are eliminated through the process of programmed cell death. FDC which are intimately associated with the GC B cells are thought to be important in this selection process. Previously, we have shown that the LFA-1 (CD11a/CD18)-ICAM-1 (CD54) and VLA-4 (CD49d)-VCAM-1 (CD106) adhesion pathways are involved in FDC-B cell interaction. In the present study, we have explored whether these adhesive interactions contribute to the process of B cell selection by studying the effects on apoptosis of GC B cells. Using FDC and B cells derived from human tonsils, we found that only B cells adherent to FDC remain viable: disruption of FDC-B-cell clusters with mAb against LFA-1 alpha (CD11a), VLA-4 (CD49d), ICAM-1 (CD54), or VCAM-1 (CD106) results in apoptosis of the B cells. Furthermore, we found that GC B cells, upon adhesion to plastic-coated purified ICAM-1 (CD54) or VCAM-1 (CD106), show diminished apoptosis. Importantly, we observed that, at low concentration, ICAM-1 (CD54) and VCAM-1 (CD106) act synergistically with anti-IgM, in inhibiting apoptosis. Together, our data strongly suggest that adhesion of B cells via the LFA-1 (CD11a/CD18)-ICAM-1 (CD54) pathway and VLA-4 (CD49d)-VCAM-1 (CD106) pathway contributes to B cell selection.
Koopman
G
G
Department of Pathology, University of Amsterdam, The Netherlands.
Keehnen
R M
RM
Lindhout
E
E
Newman
W
W
Shimizu
Y
Y
van Seventer
G A
GA
de Groot
C
C
Pals
S T
ST
D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002648:Child; D003713:Dendritic Cells / Q000166:cytology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D014066:Palatine Tonsil / Q000166:cytology*; D016029:Receptors, Very Late Antigen / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D016029:Receptors, Very Late Antigen; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1