AID-expressing germinal center B cells cluster normally within lymph node follicles in the absence of FDC-M1+ CD35+ follicular dendritic cells but dissipate prematurely.
Upon activation with T-dependent Ag, B cells enter germinal centers (GC) and upregulate activation-induced deaminase (AID). AID(+) GC B cells then undergo class-switch recombination and somatic hypermutation. Follicular dendritic cells (FDC) are stromal cells that underpin GC and require constitutive signaling through the lymphotoxin (LT) β receptor to be maintained in a fully mature, differentiated state. Although it was shown that FDC can be dispensable for the generation of affinity-matured Ab, in the absence of FDC it is unclear where AID expression occurs. In a mouse model that lacks mature FDC, as well as other LT-sensitive cells, we show that clusters of AID(+)PNA(+)GL7(+) Ag-specific GC B cells form within the B cell follicles of draining lymph nodes, suggesting that FDC are not strictly required for GC formation. However, later in the primary response, FDC-less GC dissipated prematurely, correlating with impaired affinity maturation. We examined whether GC dissipation was due to a lack of FDC or other LTβ receptor-dependent accessory cells and found that, in response to nonreplicating protein Ag, FDC proved to be more critical for long-term GC maintenance. Our study provides a spatial-temporal analysis of Ag-specific B cell activation and AID expression in the context of a peripheral lymph node that lacks FDC-M1(+) CD35(+) FDC and other LT-sensitive cell types, and reveals that FDC are not strictly required for the induction of AID within an organized GC-like environment.
Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Bryant
B
Boulianne
Michael X
MX
Le
Lesley A
LA
Ward
Lingjin
L
Meng
Dania
D
Haddad
Conglei
C
Li
Alberto
A
Martin
Jennifer L
JL
Gommerman
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003564:Cytidine Deaminase / Q000096:biosynthesis / Q000378:metabolism*; D020566:Dendritic Cells, Follicular / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D053259:Lymphotoxin beta Receptor / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017463:Receptors, Complement 3b / Q000378:metabolism; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D053259:Lymphotoxin beta Receptor; D017463:Receptors, Complement 3b; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase