ABSTRACT
A panel of monoclonal antibodies specific for a corresponding panel of sequentially selected variants of influenza A/PR/8/34 virus has been established. Although the monoclonal antibodies are paratypically distinct, idiotypic relatedness has been observed. Two cross-reactive idiotypes have been defined that are associated with the 7183 and S107 VH gene families, respectively. Three of the four monoclonal antibodies utilize the VK21 group of light chains, and three VH genes belong to the VH7183 family and one to the VH S107 family. Antibodies encoded by genes deriving from the VH7183 family share a cross-reactive idiotype, a marker of the VH region as well as distinct individual idiotopes. These antibodies are produced by different clones using related VH and VK genes.
Subject(s)
Antibodies, Monoclonal/analysis , Antibodies, Viral/analysis , Antibody Specificity , Influenza A virus/immunology , Animals , Antibodies, Monoclonal/biosynthesis , Antibodies, Viral/biosynthesis , Epitopes/immunology , Genetic Variation , Hemagglutinin Glycoproteins, Influenza Virus , Hemagglutinins, Viral/genetics , Hemagglutinins, Viral/immunology , Immunoglobulin Heavy Chains/genetics , Immunoglobulin Heavy Chains/immunology , Immunoglobulin Idiotypes/genetics , Immunoglobulin Idiotypes/immunology , Immunoglobulin Variable Region/genetics , Influenza A virus/genetics , Mice , Mice, Inbred BALB C , RabbitsABSTRACT
The secondary and tertiary immune responses to TNP-KLH and the autoanti-immunoglobulin response were studied in 1-, 3- and 6-month-old 129/J and 129/Sv mice. A profound inability of aging 129/Sv mice (lifespan: 9 months) to produce gamma 2a anti-TNP antibodies relative to their normal counterparts was observed. However, this markedly low response could not be related to clearance of antibody by RFs since all 129 mice studied produced significant amounts of RFs after immunization with this T-dependent antigen. Furthermore, the results of the plaque forming cell assays indicated that young (1 month old) 129/Sv mice have an accelerated immune response while older mice produce significantly low direct and indirect responses compared to the control groups. The data suggest a fundamental dysfunction of B and/or T cells in 129/Sv mice and that spontaneous production of RFs in older mice may affect the ability of B and T cells to cooperate in a secondary response.
Subject(s)
Antibodies, Anti-Idiotypic/biosynthesis , Immunoglobulin G , Rheumatoid Factor/biosynthesis , Aging , Animals , B-Lymphocytes/immunology , Immunization, Secondary , Immunoglobulin Idiotypes , Lymphocyte Cooperation , Mice , Mice, Inbred Strains , T-Lymphocytes/immunology , Trinitrobenzenes/immunologyABSTRACT
The nature of the immune response to two conventional polysaccharide thymus-independent (TI) antigens was investigated in two RF-producing mouse strains, the 129/Sv and MRL/1 pr, as well as in their normal congenic counterparts, 129/J and MRL +/+ animals. An age-dependent variation of clones specific for the TI-2 antigens bacterial levan (BL) and alpha 1, 3 dextran B1355 (Dex) was observed in 129/J mice. Surprisingly, the anti-BL and anti-Dex responses observed for young (1-mo-old) 129/Sv mice far exceeded those of their age-matched controls indicating an accelerated ontogenic development of the immune response to TI-2 antigens. A poor response was observed for both MRL +/+ and MRL/1 pr mice after immunization with BL. More importantly, MRL mice, unlike other H-2k, Igh.Ca strains, were unresponsive to Dex in CFA or saline. MRL mice, however, could respond to the T-dependent form of this antigen, Dex-KLH, suggesting that these mice lack the subset of B cells required to respond to TI-2 antigens. Finally, the most striking observation was the occurrence of isotype-specific RF subsequent to immunization with these antigens in animals prone to develop RF, as well as in aged animals that do not spontaneously produce RF.
