Differential regulation of expression of the MHC class II molecules RT1.B and RT1.D on rat B lymphocytes: effects of interleukin-4, interleukin-13 and interferon-gamma.
Susceptibility to induction of both T helper 1- (Th1) and Th2-mediated autoimmunity is multifactorial and involves genetic linkage to the major histocompatibility complex (MHC) class II haplotype. Brown Norway (BN) rats exposed to mercuric chloride develop a Th2-dependent systemic autoimmunity, whereas Lewis rats, which are highly susceptible to Th1-mediated autoimmunity, develop immune suppression after mercuric chloride exposure. Exposure to mercuric chloride is known to enhance B-lymphocyte expression of the MHC class II molecule RT1.B, predominantly in BN rats. We demonstrate that, in contrast, expression of RT1.D was unmodified on these B cells, whereas both RT1.B and RT1.D were up-regulated on epithelial cells. Regulation of B-cell MHC class II isotype expression was further studied in vitro, using BN rat lymph node (LN) cells. Interleukin-4 (IL-4) strongly enhanced B-cell expression of RT1.B (2.8-fold), whereas RT1.D expression was only slightly, although significantly, modified (1.2-fold). B cells from Lewis rats showed a similar IL-4-induced enhancement of RT1.B expression (2.5-fold), whereas, in contrast, RT1.D expression was unmodified. Exposure of LN cells from BN rats to interferon-gamma induced a moderate increase of B-cell MHC class II expression, predominantly of RT1.B. Strong and rapid enhancement of B-cell RT1.D expression was observed after stimulation by phorbol 12-myristate 13-acetate and ionomycin. Rat IL-13 did not modify B-cell MHC class II expression; however, it induced typical morphological changes in peritoneal macrophages. These experiments demonstrate isotype-specific and strain-dependent regulation of MHC class II expression on rat B lymphocytes, which may be of pathophysiological relevance for the strain-dependent susceptibility for Th1- or Th2-mediated autoimmunity.
Roos
A
A
Department of Pathology, Academic Medical Centre, Amsterdam, The Netherlands.
Schilder-Tol
E J
EJ
Chand
M A
MA
Claessen
N
N
Lakkis
F G
FG
Pascual
D W
DW
Weening
J J
JJ
Aten
J
J
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D018929:Cell Culture Techniques; D016207:Cytokines / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D006649:Histocompatibility Antigens / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000276:immunology; D018793:Interleukin-13 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D015759:Ionomycin / Q000276:immunology; D008627:Mercuric Chloride / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000276:immunology
D016207:Cytokines; D006649:Histocompatibility Antigens; D018793:Interleukin-13; D011994:Recombinant Proteins; C038353:histocompatibility antigens RT, rat; D015847:Interleukin-4; D008627:Mercuric Chloride; D015759:Ionomycin; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate