Decreased expression of Kruppel-like factors in memory B cells induces the rapid response typical of secondary antibody responses

Authors:
Good KL, Tangye SG
In:
Source: Proc Natl Acad Sci USA
Publication Date: (2007)
Issue: 104(33): 13420-5
Research Area:
Immunotherapy / Hematology
Cells used in publication:
B cell, human
Species: human
Tissue Origin: blood
Platform:
Nucleofector™ I/II/2b
Abstract
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 naܯve 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 naܯve cells express higher levels than memory B cells of Krüppel-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 naܯve 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.