A new murine model of humoral immuno-deficiency specifically affects class switching to T-independent antigens.
Immunoglobulin (Ig) isotype deficiencies are among the most common and least characterized humoral immunodeficiencies. A thorough understanding of their immunological and genetic features has been hampered by their extreme heterogeneity and the paucity of suitable animal models. Here, we report the initial characterization of a new mouse model with selective Ig deficiency. SENCARA mice display low serum IgG3 levels as well as severely deficient IgG3 responses to T cell-independent (TI) type 1 and 2 antigens. However, despite the significant block in class switching, expression of activation-induced deaminase and gamma3 germ-line transcription after TI antigen immunization are normal. IgG3 production in response to in vitro LPS stimulation was also normal, ruling out a specific defect in the Cgamma3 switch machinery. A decrease in the number of peritoneal B1a cells and enlarged splenic marginal zones were observed. The immunodeficiency is inherited as an autosomal, semi-dominant, essentially monogenic trait in SENCARA x C57BL/6 crosses. The SENCARA humoral immunodeficiency constitutes a novel immune phenotype, resembling human conditions such as IgG2 deficiency. This new mouse model will be of interest for the understanding of mechanisms involved in TI immune responses and may provide new insights into the molecular basis of human Ig deficiencies.
Kuzin
Igor I
II
Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester 14625, USA.
Ugine
Gregory D
GD
Barth
Richard K
RK
Shultz
Leonard D
LD
Nahm
Moon H
MH
Young
Faith M
FM
Bottaro
Andrea
A
D000818:Animals; D000955:Antigens, T-Independent / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002455:Cell Division; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000097:blood / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D018632:Mice, Inbred SENCAR; D018448:Models, Immunological; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000955:Antigens, T-Independent; D007074:Immunoglobulin G