bcl-2 Transgene Expression Inhibits Apoptosis in the Germinal Center and Reveals Differences in the Selection of Memory B Cells and Bone Marrow Antibody-Forming Cells

Autor: Lorraine A. O'Reilly, Andreas Strasser, David M. Tarlinton, Kenneth G. C. Smith, Soon-Meng Ang, Amanda Light
Rok vydání: 2000
Předmět:
Programmed cell death
plasma cell
Transgene
Immunology
Immunoglobulin Variable Region
Gene Expression
Apoptosis
Bone Marrow Cells
Mice
Transgenic
Biology
Antibodies
Affinity maturation
Mice
03 medical and health sciences
NAD+ Nucleosidase
0302 clinical medicine
Antigen
Antigens
CD
In Situ Nick-End Labeling
medicine
Animals
Immunology and Allergy
somatic mutation
ADP-ribosyl Cyclase
030304 developmental biology
affinity maturation
B-Lymphocytes
B cell
0303 health sciences
Membrane Glycoproteins
immunologic memory
CD40
Germinal center
Germinal Center
ADP-ribosyl Cyclase 1
Antigens
Differentiation
Molecular biology
Genes
bcl-2
Mice
Inbred C57BL
medicine.anatomical_structure
Proto-Oncogene Proteins c-bcl-2
Mutation
biology.protein
Immunization
Original Article
Bone marrow
Antibody
030215 immunology
Zdroj: The Journal of Experimental Medicine
ISSN: 1540-9538
0022-1007
DOI: 10.1084/jem.191.3.475
Popis: Immunization with T cell–dependent antigens generates long-lived memory B cells and antibody-forming cells (AFCs). Both populations originate in germinal centers and, predominantly, produce antibodies with high affinity for antigen. The means by which germinal center B cells are recruited into these populations remains unclear. We have examined affinity maturation of antigen-specific B cells in mice expressing the cell death inhibitor bcl-2 as a transgene. Such mice had reduced apoptosis in germinal centers and an excessive number of memory B cells with a low frequency of V gene somatic mutation, including those mutations encoding amino acid exchanges known to enhance affinity. Despite the frequency of AFCs being increased in bcl-2–transgenic mice, the fraction secreting high-affinity antibody in the bone marrow at day 42 remained unchanged compared with controls. The inability of BCL-2 to alter selection of bone marrow AFCs is consistent with these cells being selected within the germinal center on the basis of their affinity being above some threshold rather than their survival being due to a selective competition for an antigen-based signal. Continuous competition for antigen does, however, explain formation of the memory compartment.
Databáze: OpenAIRE
Externí odkaz: