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F Willems

Publications and source records attributed to F Willems.

46 records · Page 3Linked to original sources
PubMed1990

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.

Animals↗
PubMed1990

A private idiotype can become recurrent through genetic recombination and gene(s) unlinked to the Igh locus governs its expression.

Any immune response is characterized by its idiotypic profile. Two different kinds of idiotype (Id) have been described. Private Id are restricted to a few individuals from a species while recurrent Id appear in a large majority of individuals from the same species immunized with the same antigen. We describe, in this report, an experimental model whereby a private Id can become recurrent through genetic recombination. The immune response of A mice against the hapten arsonate is characterized by a recurrent Id called cross-reactive idiotype A (CRIA). A strongly CRI, called CRIA-like, can be occasionally detected in some BALB/c mice (5% to 10%) immunized with arsonate. Molecular studies show that CRIA and CRIA-like antibodies have highly homologous D segments and identical light chains. By contrast, their VH segments are vastly dissimilar. We have examined the anti-arsonate response of inbred strains of mice whose Igh loci are recombinant between those of A/He and BALB/c. Interestingly, we have observed that the CRIA-like Id which is private in BALB/c becomes recurrent in the AXC-1 strain which harbors the VH genes from BALB/c, the DH and CH genes from A/He. Structural studies demonstrate that highly homologous, VH, VL and D segments are used in BALB/c and AXC-1 mice. The basis for this differential expression of highly similar genes could be linked to the DH locus. However, F1 mice stemming from the cross between AXC-1 and BALB/c do not express the Id. The backcross analysis shows that the non-expression of the Id in F1 mice depends on genes unlinked to the Igh locus.

Animals↗
PubMed1986

Anti-idiotypic treatment of BALB/c mice induces CRIa-bearing suppressor cells with altered Igh-restricted function.

The ABA-specific antibody response of A/J mice (Igh Ie) is dominated by the CRIa idiotype. In contrast, BALB/c mice (Igh Ia) do not produce CRIa-bearing anti-ABA antibodies after antigenic challenge. We have shown previously that treatment with rabbit anti-CRIa (R-anti-CRIa) induces the expression of "CRIa-like" anti-arsonate antibodies in BALB/c mice. In the present report, we demonstrate that R-anti-CRIa treatment enables BALB/c mice to respond to A/J ABA-specific first-order suppressor molecules (TsF1). Manipulated BALB/c also produced CRIa bearing ABA-specific immune response. Thus, R-anti-CRIa treatment induces a change in the characteristic Igh restriction pattern typically seen in this system. These data suggest that Igh restriction in the ABA-specific T suppressor cell pathway is the result of CRIa+ dominance in the T suppressor cell response of A/J mice. The effectiveness of idiotypic manipulation in inducing the expression of a given idiotype at both the B cell and T suppressor cell levels is discussed.

Animals↗