AID constrains germinal center size by rendering B cells susceptible to apoptosis.
The germinal center (GC) is a transient lymphoid tissue microenvironment that fosters T cell-dependent humoral immunity. Within the GC, the B cell-specific enzyme, activation-induced cytidine deaminase (AID), mutates the immunoglobulin locus, thereby altering binding affinity for antigen. In the absence of AID, larger GC structures are observed in both humans and mice, but the reason for this phenomenon is unclear. Because significant apoptosis occurs within the GC niche to cull cells that have acquired nonproductive mutations, we have examined whether a defect in apoptosis could account for the larger GC structures in the absence of AID. In this report, we reveal significantly reduced death of B cells in AID(-/-) mice as well as in B cells derived from AID(-/-) bone marrow in mixed bone marrow chimeric mice. Furthermore, AID-expressing B cells show decreased proliferation and survival compared with AID(-/-) B cells, indicating an AID-mediated effect on cellular viability. The GC is an etiologic site for B-cell autoimmunity and lymphomagenesis, both of which have been linked to aberrant AID activity. We report a link between AID-induced DNA damage and B-cell apoptosis that has implications for the development of B-cell disorders.
Zaheen
Ahmad
A
Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
Boulianne
Bryant
B
Parsa
Jahan-Yar
JY
Ramachandran
Shaliny
S
Gommerman
Jennifer L
JL
Martin
Alberto
A
D000818:Animals; D017209:Apoptosis; D015551:Autoimmunity / Q000235:genetics; D001402:B-Lymphocytes / Q000166:cytology*; D001853:Bone Marrow; D049109:Cell Proliferation; D002470:Cell Survival; D003564:Cytidine Deaminase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004249:DNA Damage; D018858:Germinal Center / Q000166:cytology*; D016393:Lymphoma, B-Cell / Q000209:etiology / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase