Antibodies (Abs) are produced by terminally differentiated plasma cells 28Newly generated plasma cells after tamoxifen treatmentare not labeled.Blimp1-Cre-ERT2Rosa26-loxP-stop-loxP-tdTomatoTamoxifenTamoxifenA few monthslaterapoptosisLong-livedplasma cells(PCs) and have distinct effector functions depending on their isotype. While the majority of PCs generated in the secondary lymphoid organs die within days after their formation (termed short-lived PCs; SLPCs), a small ma-jority persists for months, years, or even decades. These long-lived PCs (LLPCs) are found in locations distinct from their generation site, often in the bone mar-row. Hence, in order to distinguish between SLPCs and LLPCs, previous studies determined the number of PCs residing in the bone marrow, considering them as LLPCs. However, since it is known that this bone marrow population also in-cludes recently generated SLPCs, determining the exact number of LLPCs is not possible using this approach. To overcome the limitation of the current assay system, we developed an in vivo time-stamping method for PCs, thereby allow-ing us to directly measure the decay of the labeled bone marrow PCs (Figure).Using this method, we first demonstrated that the homeostatic PC pool in the bone marrow was continuously replenished by recently arriving B220hiM-HC-IIhi cells, a small fraction of which then matured into a B220loMHC-IIlo LLPC pool. Second, in the NP-CGG immune response, contrary to expecta-tion, we could not find significant survival differences between GC-inde-pendent and -dependent NP+ PCs in the bone marrow. Finally, in contrast to NP+B220hiMHC-IIhi SLPCs in the bone marrow, the NP+B220loMHC-IIlo LLPCs with greater survival potential were more likely to be immobilized in the niches, suggesting an association between adhesion strength and provision of survival signals to PCs.Figure: Establishment of the PC time-stamping methodSchematic representation of the PC-linage tracing sys-tem using Blimp1-CreERT2 R26-LSL-tdTomato mice (up-per). By injecting tamoxifen, this experimental system allows us to carry out pulse-chase experiments. With this system, only long-lived plasma cells will be labeled as tdTomato+ (lower).Recent Major PublicationsYada Y, Matsumoto M, Inoue T, Baba A, Higuchi R, Kawai C, Yanagisawa M, Kitamura D, Ohga S, Kurosaki T, Baba Y. STIM-mediated calcium influx regulates maintenance and selection of germinal center B cells. J Exp Med 221, e20222178 (2024)Inoue T, Kurosaki T. Memory B cells. Nat Rev Immunol 24, 5-17 (2024)Koike T, Fujii K, Kometani K, Butler NS, Funakoshi K, Yari S, Kikuta J, Ishii M, Kurosaki T, Ise W. Progressive differen-tiation toward the long-lived plasma cell compartment in the bone marrow. J Exp Med 220, e20221717 (2023)Invited presentationsKurosaki T. “Requirement for optimal BCR signal strength in efficient positive selection of germinal center (GC) B cells” Cold Spring Harbor Asia: Immunoreceptor Sig-naling and Therapeutic Applications (Suzhou, China) November 2023Kurosaki T. “Generation mechanisms of humoral mem-ory compartments” The Immune Alliance: A German-Japanese Cooperation in Immunology (Berlin, Germany/Online) October 2023Kurosaki T. “Regulation of plasma cell egress from secondary lymphoid tissues and its retention in bone marrow” Keystone Symposia: T and B Cell Collaboration in Germinal Centers and Beyond (Whistler, Canada) October 2023Kurosaki T. “Fate Decision mechanism of germinal center (GC) B cell” Finnish-Japanese Immunology Symposium (Turku, Finland) August 2023Kurosaki T. “Requirement for optimal BCR signal strength in efficient positive selection of germinal center (GC) B cells” Keystone Symposia: B Cell Biology in the Context of Infectious Diseases, Autoimmunity and B Cell Cancers (Keystone, USA) June 2023Laboratory for Lymphocyte DifferentiationTeam Leader: Tomohiro Kurosaki
元のページ ../index.html#34