The antiphosphocholine (PC) antibody in normal mouse sera (NMS) provides protection against intravenous infection with encapsulated strain WU2 of type 3 Streptococcus pneumoniae. Mice unable to make anti-PC antibody, as a result of suppression with anti-T-15 idiotype or inheritance of the xid gene of CAB/N mice, are highly susceptible to infection with strain WU2. Mice inheriting the xid gene can be protected with NMS from immunologically normal mice or with IgM hybridoma anti-PC antibody. The protective effect of NMS can be removed with PC-containing immunoabsorbents.
Antigens have been classified previously into three categories, thymus-dependent (TD), thymus-independent type (TI) 1, and TI-2, based upon thymic dependence and ability to stimulate an immunodeficient strain of mouse, CBA/N. Here we demonstrate that the different antigen classes elicit IgG antibodies of different subclasses. TD antigens stimulate predominantly IgG1 antibodies, with smaller amounts of IgG2 and IgG3 being expressed. TI-1 antigens stimulate almost no IgG1 antibodies and equal amounts of IgG2 and IgG3. TI-2 antigens elicit predominantly IgG3 antibodies. Mice expressing the CBA/N phenotype are known to be nonresponsive to TI-2 antigens. This was confirmed in this study. In addition, we demonstrate that the IgG3 component of the response to TI-1 antigens is virtually absent in mice expressing the CBA/N phenotype, which supports our previous finding that the CBA/N defect may be restricted to a B-lymphocyte subpopulation containing most of the precursors of IgG3-secreting cells.
The complete variable region sequences from ten antibodies and two myeloma proteins binding alpha-1,3 dextran have been determined. The diversity patterns of these homogeneous antibody molecules suggest that the variable regions of heavy chains are encoded by separate variable (V) and joining (J) gene segments. The most striking feature of these data is the extensive sequence variability of a region that we denote the D (diversity) segment which is located at the junction between the V and J segments in the centre of the third hypervariable region. The D segment diversity may arise from a novel somatic mutational mechanism or may be encoded by multiple D gene segments. For the first time, the amino acid sequence correlates of several V region idiotypes are determined.
Isolated rat islets remain morphologically and functionally intact during a 7-day period of in vitro culture at 24 degrees C. In vitro culture of islets at 24 degrees C for 7 days prior to transplantation, in conjunction with a single injection of antiserum to lymphocytes into the diabetic recipient, results in islet allograft survival of 100 days when the islets are transplanted across a major histocompatibility barrier.
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