A new murine model of humoral immuno‐deficiency specifically affects class switching to T‐independent antigens

Abstract

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 + 3 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 C + 3 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, semidominant, essentially monogenic trait in SENCARA × 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.

Asbestos activates CH12.LX B-lymphocytes via macrophage signaling

“…The IgG 3 sub-class, if autoreactive, has demonstrated the potential of developing diseases ranging from glomerulonephritis to SLE as complement has a strong affinity towards the constant region of all IgG 3 sub-classes (Fulpius et al, 1993; Baudino et al, 2006). The production of IgA by this B1a B-lymphocyte model has been reported in response to various cytokines or LPS (Bao et al, 1999; Kuzin et al, 2004), and is consistent with the fact that B1a B-lymphocytes are responsible for producing the majority of IgA within the gut and lamina propria (Kroese et al, 1989, 1993). This further supports the use of CH12.LX cells as a model for studying the antigen-independent signaling responses by B1a B-lymphocytes that result in immunoglobulin production.…”

Immunodeficiency Accelerates Vitamin A Deficiency

“…We then extended these studies to a model of humoral immunodeficiency, the SENCAR mouse ( 26 ). These mice derive their name from the characteristic superior sensitivity to chemical and viral carcinogens ( 24 , 37 ).…”

“…We also used the SENCAR (SENsitive to CARcinogenesis) mouse, a model used widely to study the effectiveness of different biological and synthetic compounds as initiating or tumor-promoting agents ( 24 ). Its susceptibility to chemical carcinogens and tumor promoters ( 25 ) may be related to its immunodeficiency, which specifically affects class switching to T-independent antigens ( 26 ).…”