Loss of a major idiotype (CRIA) after repopulation of irradiated mice.

The normal immune response of A/J mice against arsonate coupled to hemocyanin is characterized by a major recurrent cross-reactive Id, the CRIA. This Id is encoded by a single gene segment combination: VHidcr11-DFL16.1e-JH2 for the H chain and Vkidcr-Jk1 for the L chain. In this report, we show that lethal irradiation of A/J mice followed by reconstitution with autologous or syngeneic lymphoid cells results in loss of major CRIA Id expression in the response to arsonate. Different protocols were performed to repopulate the irradiated mice. First, lethally irradiated A/J mice were reconstituted by the transfer of syngeneic bone marrow cells. Second, A/J mice were lethally irradiated while their hind limbs were partially shielded. Third, lethally irradiated A/J mice received a transfer of syngeneic spleen cells. The three groups of mice produce high titers of antiarsonate antibodies completely devoid of CRIA DH-JH related idiotopes expression. Moreover, a lack of affinity maturation is observed in the secondary antiarsonate response of all irradiated and reconstituted mice. A transfer of syngeneic peritoneal cells or a transfer of primed T cells in irradiated and reconstituted A/J mice do not restore in a significant manner either the recurrent CRIA expression or the affinity maturation of the antiarsonate response. Our data suggest that the choice of this Id is not solely dictated by the Igh locus.

Enhanced inflammatory responses in alpha-tocopherol transfer protein null mice

The liver preferentially secretes alpha-tocopherol into plasma under the control of the hepatic alpha-tocopherol transfer protein (alpha-TTP). alpha-TTP-null mice (Ttpa(-/-) mice) are vitamin E deficient, therefore were used for investigations of in vivo responses to sub-normal tissue alpha-tocopherol concentrations during inflammation. Increased basal oxidative stress in Ttpa(-/-) mice was documented by increased plasma lipid peroxidation, and superoxide production by bone marrow-derived neutrophils stimulated in vitro with phorbol 12-myristate 13-acetate. Lipopolysaccharide (LPS) injected intraperitoneally induced increases in lung and liver HO-1 and iNOS, as well as plasma NO(x) in Ttpa(+/+) mice. LPS induced more modest increases in these markers in Ttpa(-/-) mice, while more marked increases in plasma IL-10 and lung lavage TNF alpha were observed. Taken together, these results demonstrate that alpha-tocopherol is important for proper modulation of inflammatory responses and that sub-optimal alpha-tocopherol concentrations may derange inflammatory-immune responses.