IgG isotype distribution of local and systemic immune responses induced by influenza virus infection

Abstract

The IgG isotype profile of the influenza virus-specific immune response was studied by quantitation of serum antibody (Ab) levels in correlation with the enumeration of antibody-secreting cells (ASC) detected in the lung, spleen, mediastinal lymph nodes (MLN), Peyer's patches and bone marrow (BM). Distinct isotypic patterns for serum Ab and Ab produced by cells present at or close to the site of infection were found after primary or repeated infections. An elevated number of IgM ASC was found after primary challenge in the spleen, lung and MLN. In contrast, the site of IgA and IgG production is restricted to the lung and lymph nodes draining the site of infection. In these organs IgA, IgG2a and IgG1 ASC are found as a result of primary virus infection while viral challenge induces mostly activation of IgA-producing cells and secretion of IgA to the lung lavage. In contrast, the majority (80-90%) of Ab detected in the serum belong to the IgG2a subclass and their serum level is maintained at a high level during the whole period of the response. The relative level of virus-specific serum IgG2a in correlation with the production of IgG2a Ab found predominantly in MLN and lung is highly dependent on the viral dose used for priming or challenge. As IgG2a ASC can be detected at relatively low numbers in the spleen and BM these results suggest that the production of the dominant IgG2a isotype of serum Ab occurs close to the viral challenge site. These data, however, point to distinct isotypic regulation in systemic versus local virus-specific Ab responses.

Kinetics of the avian influenza-specific humoral responses in lung are indicative of local antibody production

“…Following secondary infection AIV-specific IgM ASC were rarely detected, due to isotype switching and differentiation of B cells to IgY and IgA ASC. Indeed IgY and IgA responses were dominant in our experiments consistent with results found in influenza-infected mice (Fazekas et al, 1994;Justewicz et al, 1995), and horses (Nelson et al, 1998) and with kinetics of humoral immune responses in different primary and secondary infection models in chicken (Al-Garib et al, 2003;Beal et al, 2004;Marcos-Atxutegi et al, 2009;Pei and Collisson, 2005). Serum IgY is detected from 7 days following Ascaridia galli infection (Marcos-Atxutegi et al, 2009) and also Salmonella typhimurium infection (Beal et al, 2004).…”

Priming of helper T cell‐dependent antibody responses by hemagglutinin‐transgenic B cells

“…Mice that were immunized with UV-inactivated PR8 virus showed high titers of IgG2a followed by IgG3, IgG2b and IgGl (Fig. 5C) which is in accordance with earlier results by others [22,23]. Together, these data show that HA-transgenic activated B cells elicit a Th2-related IgG antibody pattern which is different to the one induced by PR8 virus.…”

Roles of CD4+T-Cell-Independent and -Dependent Antibody Responses in the Control of Influenza Virus Infection: Evidence for Noncognate CD4+T-Cell Activities That Enhance the Therapeutic Activity of Antiviral Antibodies

“…Nevertheless, the fact that the 50% lethal doses (LD 50 s) of three distinct virus strains-the highly pathogenic A/PR/8/34 (H1N1) (18) and A/Japan/305 (H2N2) (21) and the minimally pathogenic plasmid-generated H3N2 reassortant HK-RG (62) strains-were decreased Ն10-fold in B-cell-deficient compared to intact mice provides strong support for the notion that B cells make an important contribution to the control of the primary infection in the intact mouse, although additional defects in B-cell-deficient mice, such as the poor development of splenic T-cell zones and reduced splenic T-cell numbers (47) and possible defects in airway-associated lymphoid tissues (19) and in CD4 ϩ T cells (4,39), may also contribute to their low resistance to influenza virus infection. A significant role of B cells in the resolution of the infection is consistent also with the kinetics of the primary antibody (Ab) response, whose rise coincides with virus clearance (15,24,34,58).…”