A proliferation-inducing ligand sustains the proliferation of human naïve (CD27⁻) B cells and mediates their differentiation into long-lived plasma cells in vitro via transmembrane activator and calcium modulator and cyclophilin ligand interactor and B-cell mature antigen.
Yoshiko Matsuda: Department of Transplant Immunology, Nagoya University School of Medicine, Nagoya, Japan.
Masataka Haneda: Department of Transplant Immunology, Nagoya University School of Medicine, Nagoya, Japan. Electronic address: m-haneda@med.nagoya-u.ac.jp.
Kenji Kadomatsu: Department of Biochemistry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Takaaki Kobayashi: Department of Transplant Immunology, Nagoya University School of Medicine, Nagoya, Japan.
Long-lived plasma cells (PCs) contribute to humoral immunity through an undefined mechanism. Memory B cells, but not human naïve B cells, can be induced to differentiate into long-lived PCs in vitro. Because evidence links a proliferation-inducing ligand (APRIL), a tumor necrosis factor family member, to the ability of bone marrow to mediate long-term PC survival, we reasoned that APRIL influences the proliferation and differentiation of naïve B cells. We describe here the development of a simple cell culture system that allowed us to show that APRIL sustained the proliferation of naïve human B cells and induced them to differentiate into long-lived PCs. Blocking the transmembrane activator and calcium modulator and cyclophilin ligand interactor or B-cell mature antigen shows they were required for the differentiation of naïve B cells into long-lived PCs in vitro. Our in vitro culture system will reveal new insights into the biology of long-lived PCs.
