Interleukin 4 Reduces Expression of Inhibitory Receptors on B Cells and Abolishes CD22 and FcγRII-mediated B Cell Suppression
Open Access
- 15 April 2002
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 195 (8), 1079-1085
- https://doi.org/10.1084/jem.20011435
Abstract
Inhibitory receptors CD22, FcγRII (CD32), CD72, and paired immunoglobulin-like receptor (PIR)-B are critically involved in negatively regulating the B cell immune response and in preventing autoimmunity. Here we show that interleukin 4 (IL-4) reduces expression of all four on activated B cells at the level of messenger RNA and protein. This reduced expression is dependent on continuous exposure to IL-4 and is mediated through Stat6. Coligation of FcγRII to the B cell receptor (BCR) via intact IgG increases the B cell activation threshold and suppresses antigen presentation. IL-4 completely abolishes these negative regulatory effects of FcγRII. CD22 coligation with the BCR also suppresses activation — this suppression too is abolished by IL-4. Thus, IL-4 is likely to enhance the B cell immune response by releasing B cells from inhibitory receptor suppression. By this coordinate reduction in expression of inhibitory receptors, and release from CD22 and FcγRII-mediated inhibition, IL-4 is likely to play a role in T cell help of B cells and the development of T helper cell type 2 responses. Conversely, B cell activation in the absence of IL-4 would be more difficult to achieve, contributing to the maintenance of B cell tolerance in the absence of T cell help.Keywords
This publication has 31 references indexed in Scilit:
- Immune Inhibitory ReceptorsScience, 2000
- CD72, a negative regulator of B‐cell responsivenessImmunological Reviews, 2000
- Spontaneous Autoimmune Disease in FcγRIIB-Deficient Mice Results from Strain-Specific EpistasisImmunity, 2000
- Autoimmune-prone mice share a promoter haplotype associated with reduced expression and function of the Fc receptor FcγRIICurrent Biology, 2000
- THE IL-4 RECEPTOR: Signaling Mechanisms and Biologic FunctionsAnnual Review of Immunology, 1999
- Constitutive Expression of Interleukin (IL)-4 In Vivo Causes Autoimmune-type Disorders in MiceThe Journal of Experimental Medicine, 1997
- Characterization of the expression and gene promoter of CD22 in murine B cellsEuropean Journal of Immunology, 1996
- Hyperresponsive B Cells in CD22-Deficient MiceScience, 1996
- Augmented humoral and anaphylactic responses in FcγRII-deficient miceNature, 1996
- A Role in B Cell Activation for CD22 and the Protein Tyrosine Phosphatase SHPScience, 1995