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TACI is required for the survival of short- and long-lived plasma cells
Kenji Funakoshi1,2, Takuya Koike1,3,4, Wataru Ise1,4,5
1Laboratory of Lymphocyte Differentiation, World Premier International Research Center Initiative (WPI), Immunology Frontier Research Center (IFReC), The University of Osaka, Suita, Osaka 565-0871, Japan.
In a typical immune response, naïve B cells are activated, differentiated into short-lived plasma cells (SLPCs), and then matured into long-lived plasma cells (LLPCs) in the bone marrow. Among three TNF family receptors (BAFF-R, TACI, and BCMA), BAFF-R and BCMA are known to be crucial for the maintenance of naïve B cells and bone marrow LLPCs, respectively. In contrast, the function of TACI remains unclear, as analysis of global TACI knockout mice suggests the existence of two opposing roles in B and plasma cells. Here, to define the role of TACI during T cell-dependent (TD) immune responses in a B and plasma cell-intrinsic manner, we utilized adoptive transfer experiments employing B cells with a conditional TACI knockout. We show that B cell activation is apparently normal in the absence of TACI, while it is crucial for the expansion of IgM+ and IgG1+ SLPCs and maintenance of their resultant bone marrow LLPCs. Hence, our data suggest that the hyper-B cell activation seen in global TACI knockout mice could be due to an indirect control of BAFF levels or B cell extrinsic anomalies.
In a typical immune response, naïve B cells are activated, differentiated into short-lived plasma cells (SLPCs), and then matured into long-lived plasma cells (LLPCs) in the bone marrow. Among three TNF family receptors (BAFF-R, TACI, and BCMA), BAFF-R and BCMA are known to be crucial for the maintenance of naïve B cells and bone marrow LLPCs, respectively. In contrast, the function of TACI remains unclear, as analysis of global TACI knockout mice suggests the existence of two opposing roles in B and plasma cells. Here, to define the role of TACI during T cell-dependent (TD) immune responses in a B and plasma cell-intrinsic manner, we utilized adoptive transfer experiments employing B cells with a conditional TACI knockout. We show that B cell activation is apparently normal in the absence of TACI, while it is crucial for the expansion of IgM+ and IgG1+ SLPCs and maintenance of their resultant bone marrow LLPCs. Hence, our data suggest that the hyper-B cell activation seen in global TACI knockout mice could be due to an indirect control of BAFF levels or B cell extrinsic anomalies.
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