Expression of IL-9 receptor alpha chain on human germinal center B cells modulates IgE secretion.
BACKGROUND
IL-9 has been shown to affect the differentiation pathway of different cell types. However, its potential role in the maturation pathway of antigen-driven B-cell differentiation and its functional effects remain unknown.


OBJECTIVE
To characterize IL-9 receptor alpha chain (IL-9R alpha) expression on human tonsillar B cells at different maturational stages, and to assess its effect on IgE production.


METHODS
Freshly purified human tonsillar B cells were fractionated into 3 populations: low-density (LD), medium-density, and high-density cells. Expression levels of IL-9R alpha were determined by using immunohistochemistry and flow cytometry. IL-9R alpha(high)-expressing cells were stimulated with IL-9 in the presence or absence of IL-4, and IgE release was measured by ELISA.


RESULTS
IL-9R alpha was expressed on human LD tonsillar B cells, with an ability to transduce signals through activation of signal transducer and activator of transcription 3 and 5. Although IL-9 was unable to induce IgE secretion by itself, it potentiated IL-4-mediated IgE production from LD cells. Moreover, increased IgE was paralleled by an upregulation of IL-9R alpha and CD27, with the latter a memory B-cell marker implicated in increased IgE secretion.


CONCLUSIONS
These results highlight a crucial role for IL-9 in modulating T-cell-dependent B-cell differentiation and establish a new paradigm for understanding the synergistic role of T(H)2 cytokines and their modulatory effect on B-cell maturation and IgE production.


CONCLUSIONS
IL-9 appears to be involved in memory B-cell differentiation and T(H)2-mediated allergic diseases such as asthma.
Fawaz
Lama M
LM
Department of Medicine, Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada.
Sharif-Askari
Ehssan
E
Hajoui
Oumnia
O
Soussi-Gounni
Abdelilah
A
Hamid
Qutayba
Q
Mazer
Bruce D
BD
D001402:B-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D002478:Cells, Cultured; D018858:Germinal Center / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D015847:Interleukin-4 / Q000494:pharmacology; D016906:Interleukin-9 / Q000494:pharmacology / Q000502:physiology; D014066:Palatine Tonsil / Q000737:chemistry / Q000276:immunology*; D010766:Phosphorylation; D053651:Receptors, Interleukin-9 / Q000032:analysis / Q000378:metabolism*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism; D015854:Up-Regulation
C508045:IL9R protein, human; D016906:Interleukin-9; D053651:Receptors, Interleukin-9; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D015847:Interleukin-4; D007073:Immunoglobulin E