Clonal anergy of CD117+chB6+ B cell progenitors induced by avian leukosis virus subgroup J is associated with immunological tolerance

Abstract

BackgroundThe pathogenesis of immunological tolerance caused by avian leukosis virus subgroup J (ALV-J), an oncogenic retrovirus, is largely unknown.ResultsIn this study, the development, differentiation, and immunological capability of B cells and their progenitors infected with ALV-J were studied both morphologically and functionally by using a model of ALV-J congenital infection. Compared with posthatch infection, congenital infection of ALV-J resulted in severe immunological tolerance, which was identified as the absence of detectable specific antivirus antibodies. In congenitally infected chickens, immune organs, particularly the bursa of Fabricius, were poorly developed. Moreover, IgM-and IgG-positive cells and total immunoglobulin levels were significantly decreased in these chickens. Large numbers of bursa follicles with no differentiation into cortex and medulla indicated that B cell development was arrested at the early stage. Flow cytometry analysis further confirmed that ALV-J blocked the differentiation of CD117+chB6+ B cell progenitors in the bursa of Fabricius. Furthermore, both the humoral immunity and the immunological capability of B cells and their progenitors were significantly suppressed, as assessed by (a) the antibody titres against sheep red blood cells and the Marek’s disease virus attenuated serotype 1 vaccine; (b) the proliferative response of B cells against thymus-independent antigen lipopolysaccharide (LPS) in the spleen germinal centres; and (c) the capacities for proliferation, differentiation and immunoglobulin gene class-switch recombination of B cell progenitors in response to LPS and interleukin-4(IL-4) in vitro.ConclusionsThese findings suggested that the anergy of B cells in congenitally infected chickens is caused by the developmental arrest and dysfunction of B cell progenitors, which is an important factor for the immunological tolerance induced by ALV-J.

Lyn inhibited BCR signal pathway mediates B-cell anergy induced by avian leukosis virus subgroup J

“…It has been found that the damage of lymphocytes [29], the abnormal secretion of cytokines [30], the variation of viral epitopes [31], and the expression of EAV-HP gene in embryo [32] all play more or less roles in the induction of immune tolerance by ALV-J. In previous study, we demonstrated that B-cell anergy induce by ALV-J should take most of the responsibility for immune tolerance [13]. After all, the antiviral neutralizing antibodies were produced by normal B-cells.…”

“…The 6-day-old embryos of Leghorn specific-pathogen-free (SPF) chickens (Jinan poultry technology company, China) were injected with ALV-J through the allantoic cavity to establish the infected group (n = 30).The control group (n = 30) was established by injecting DMEM instead of virus. The treatment of virus inoculation, chicken embryos incubation, and virus detection were all followed as our previous description [13].…”

“…The existence and identity of anergic B-cell in animal models or human have been known for some time [11,12], but the pathogenesis of B-cell anergy induced by some viruses has not been completely addressed. However, our previous studies has showed that the main cause of immune tolerance was associated with the B-cell anergy induced by ALV-J [13].…”

“…The perform of IHC test were followed as our previous description. [13]Negative controls were also performed with the…”

Immunopathogenesis and Cellular Interactions in Human T-Cell Leukemia Virus Type 1 Associated Myelopathy/Tropical Spastic Paraparesis

“…In addition, the protective effects of HLA-B ∗ 07 in Spain and HLA-A ∗ 0201 and HLA-Cw ∗ 0801 in Japan are documented as well ( Vallinoto et al, 2019 ). The predisposing effects HLA-B ∗ 5401 have been proven, but are not observed in Brazil ( Catalan-Soares et al, 2009 ; Bangham et al, 2015 ; Enose-Akahata and Jacobson, 2019 ).…”