Thymic stromal lymphopoietin (TSLP)-induced polyclonal B-cell activation and autoimmunity are mediated by CD4 super(+) T cells and IL-4

• Published in: International immunology Vol. 24; no. 3; pp. 183 - 195
• Main Authors: Iseki, Masanori, Omori-Miyake, Miyuki, Xu, Whitney, Sun, Xiaocui, Takaki, Satoshi, Rawlings, David J, Ziegler, Steven F
• Format: Journal Article
• Language: English
• Published: 01.01.2012
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/dxr113

The cytokine thymic stromal lymphopoietin (TSLP) functions as a regulator of bone marrow B-cell development and a key initiator of allergic inflammation. In the current study, we show that mature B cells, derived from transgenic mice with systemically elevated levels of TSLP (K5-TSLP mice), exhibit markedly enhanced mitogenic responses in vitro and that this enhanced responsiveness leads to polyclonal B-cell activation and development of autoimmune hemolytic anemia in vivo. In contrast, B cells derived from K5-TSLP mice lacking CD4 super(+) T cells failed to show polyclonal activation. Furthermore, neither mature B-cell activation nor hemolytic anemia occurred in IL-4-deficient K5-TSLP mice. Consistent with these findings, activation of mature B cells occurred independently of B-cell intrinsic TSLP signals. Taken together, our results demonstrate that systemic alterations in TSLP, through induction of IL-4 from CD4 super(+) T cells and other cell types, functions as an important factor in peripheral B-cell homeostasis and promotion of humoral autoimmunity.