Expression of aberrant forms of CD22 on B lymphocytes in Cd22a lupus-prone mice affects ligand binding.
CD22 functions primarily as a negative regulator of B-cell receptor signaling. The Cd22a allele has been proposed as a candidate allele for murine systemic lupus erythematosus. In this study, we explored the possible expression of aberrant forms of CD22, which differ in the N-terminal sequences constituting the ligand-binding site due to synthesis of abnormally processed Cd22 mRNA, in several Cd22a mouse strains, including C57BL/6 Cd22 congenic mice. The staining pattern of splenic B cells obtained with CY34 anti-CD22 mAb, which was expected to bind poorly to the aberrant CD22, was more heterogeneous in Cd22(a) mice than in Cd22b mice. Moreover, CD22 detected on B cells of Cd22a mice was expressed more weakly and as a smaller-sized protein, compared with Cd22b mice. Significantly, analysis with a synthetic CD22 ligand demonstrated that Cd22a mice carried a larger proportion of CD22 that was not bound by cis ligands on the B-cell surface than Cd22b mice. Finally, the study of C57BL/6 Cd22 congenic mice revealed that Cd22a B cells displayed a phenotype reminiscent of constitutively activated B cells (reduced surface IgM expression and augmented MHC class II expression), as reported for B cells expressing a mutant CD22 lacking the ligand-binding domain. Our demonstration that Cd22a B cells express aberrant forms of CD22, which can potentially deregulate B-cell signaling because of their decreased ligand-binding capacity, provides further support for Cd22a as a potential candidate allele for murine systemic lupus erythematosus.
Nitschke
Lars
L
Department of Genetics, University of Erlangen, 91058 Erlangen, Germany.
Lajaunias
Frédéric
F
Moll
Thomas
T
Ho
Liza
L
Martinez-Soria
Eduardo
E
Kikuchi
Shuichi
S
Santiago-Raber
Marie-Laure
ML
Dix
Carolin
C
Parkhouse
R Michael E
RM
Izui
Shozo
S
D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D005802:Genes, MHC Class II / Q000235:genetics / Q000276:immunology; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology; D008024:Ligands; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008814:Mice, Inbred NZB; D018345:Mice, Knockout; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics / Q000276:immunology*; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*
C497868:Cd22 protein, mouse; D007075:Immunoglobulin M; D008024:Ligands; D051918:Sialic Acid Binding Ig-like Lectin 2