期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 104, 期 33, 页码 13420-13425出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0703872104
关键词
human B cells; immunological memory; proliferation; cellular quiescence; lymphocyte activation
Secondary antibody responses are characterized by the rapid kinetics of the responding cells, including the production of larger amounts of serum Ig compared with the primary response. Memory B cells, which are responsible for this phenomenon, undergo greater proliferation and differentiation into Ig-secreting plasma cells than naive B cells. We have found that memory cells rapidly enter cell division, irrespective of extrinsic stimuli. Microarray analysis of human splenic B cells revealed that naive cells express higher levels than memory B cells of Kruppel-like factor (KLF) 4, KLF9, and promyelocytic leukemia zinc finger (PLZF), transcription factors important in maintaining cellular quiescence. These genes were down-regulated after activation through CD40 and the B cell receptor. Enforced expression of KLF4, KLF9, and PLZF in memory B cells delayed their entry into division and reduced the number of proliferating cells, such that the behavior of transfected memory cells resembled that of naive B cells. Thus, the accelerated response of memory B cells correlates with reduced expression of KLF4, KLF9, and PLZF and the subsequent regulatory effects they exert on the cell cycle.
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