CCR7-deficient mice develop atypically persistent germinal centers in response to thymus-independent type 2 antigens.
Thymus-independent type 2 (TI-2) antigens are repetitive antigens capable of eliciting antibody responses without T cell help. They are important in the immune response against encapsulated bacteria and as a rapid first line of defense against pathogens. TI-2 antigens induce strong proliferation in extrafollicular foci. However, any germinal centers forming in response to TI-2 antigens involute synchronously 5 days after immunization. This is thought to be caused by the lack of T cell help. Surprisingly, immunization of mice deficient for the homeostatic chemokine receptor CCR7 with TI-2 antigens resulted not only in the expected, vigorous extrafollicular plasma cell response but also in persisting splenic germinal centers. This was observed for two different TI-2 antigens, heat-killed Streptococcus pneumoniae and (4-hydroxy-3-nitrophenyl)acetyl-Ficoll (NP-Ficoll). Germinal centers induced by TI-2 and thymus-dependent (TD) antigens were located in the periarteriolar area of the white pulp in CCR7 knockout mice, corresponding to the T zone of wild-type (WT) mice. The TI-2-induced germinal centers contained peripheral rings of follicular dendritic cells and unusually for TI-2-induced germinal centers, T cells. The licensing responsible for their atypical persistence did not endow TI-2-induced germinal centers with the full range of characteristics of classic germinal centers induced by TD antigens. Thus, class-switching, affinity maturation, and memory B cell generation were not increased in CCR7-deficient mice. It seems unlikely that a defect in regulatory T cell (Treg) location was responsible for the atypical persistence of TI-2-induced germinal centers, as Tregs were comparably distributed in germinal centers of CCR7-deficient and WT mice.
Achtman
Ariel H
AH
Molecular Tumor Genetics and Immunogenetics, Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, Berlin, Germany.
Höpken
Uta E
UE
Bernert
Carola
C
Lipp
Martin
M
D000818:Animals; D000942:Antigens, Bacterial / Q000494:pharmacology; D000955:Antigens, T-Independent / Q000494:pharmacology*; D001402:B-Lymphocytes; D018858:Germinal Center / Q000276:immunology* / Q000473:pathology; D007156:Immunologic Memory; D018655:Lymphocyte Count; D051379:Mice; D054400:Receptors, CCR7 / Q000172:deficiency*; D050378:T-Lymphocytes, Regulatory
D000942:Antigens, Bacterial; D000955:Antigens, T-Independent; C515371:Ccr7 protein, mouse; D054400:Receptors, CCR7