Jacques Couderc

Evidence that the anti-coagulant and lethal properties of a basic phospholipase A2 from snake venom are unrelated

The basic phospholipase A2 (PLA2) from venom of the African elapid Naja nigricollis was previously shown to have anti‐coagulant and lethal properties, both of which were abolished by treatment with p‐bromophenacyl bromide (pBP). In the present paper we first report that pBP‐treated PLA2 is capable of inhibiting the anti‐coagulant activity but not the lethal activity of native PLA2, thus suggesting that both properties might be independent. We then confirm this evidence using PLA2‐specific monoclonal immunoglobulins. One of these, called HSF, neutralized the lethal activity but not the anti‐coagulant activity, whereas another antibody, called HSP2, inhibited the anti‐coagulant activity but not the lethal activity of the PLA2. The data presented in this paper are taken as evidence that the anti‐coagulant activity is not implicated in the lethal effects of basic PLA2 from Naja nigricollis.

Polymorphism of Tcrb and Tcrg genes in Biozzi mice : segregation analysis of a new Tcrg haplotype with antibody responsiveness

Tcrb andTcrg gene polymorphism was investigated in high (H) and low (L) responder Biozzi mice from selection I, II, and GS by Southern blot analysis with appropriateV andC probes. No polymorphism of theTcrb haplotype was detected between H and L mice in all selections which were all found to be of the BALB/c type. The H-I and H-II g genotype was of BALB/c and DBA/2 type, respectively. In contrast, a newTcrg haplotype shared by L-I and L-II mice was identified and characterized by Cγ1, 2, 3, Cγ4, Vγ1, 2, 3, Vγ5, and Vγ6 restriction fragment length polymorphisms (RFLPs).Tcrg genotypes were not fixed in the GS selection and two additional new haplotypes were identified in two L-GS mice. An attempt was made to correlate the L-Ig genotype with the low responder status by analyzingg haplotypes among highest and lowest responder (H-1 x L-I)F2 hybrids immunized with sheep red blood cells (SRBC). No correlation was found in this segregation study, whereas a highly significant one was established with theH-2 haplotype, a locus already known to participate in the genetic control of H-I/L-I difference. The lack of correlation between SRBC response and theTcrg genotype was consistent with the heterogenousg haplotypes found in mice of the GS selection. Together, the present results suggest that H and L mice have the sameTcrab potential repertoire and that T-cell receptor (Tcr) genes cannot be considered as immune response genes in this model. Our results also indicate that the F2 segregation analysis, given a polymorphic gene, is suitable for an investigation of its immune response functions.

Resistance to Collagen-Induced Arthritis in Biozzi Mice is Not Associated With a Defect in Autoantibodies to Accessible Epitopes on Cartilage Collagen

In order to understand why most strains of Biozzi mice are unexpectedly either arthritis‐resistant, or susceptible, we investigate the autoantibody reactivity against matrix‐embedded collagen molecules. We show a dose correlation between these tissular and the free collagen antibodies, irrespective of arthritis susceptibility. These results are against an antibody response restricted to hidden non‐pathogenic epitopes in the resistant mice.

Functional Differences in the Specific B‐Cell Compartment in High or Low Antibody Responder Mice

The role of antigen‐presenting cells (APC) in quantitative antibody synthesis regulation was studied in mice genetically selected for high (HI) or low (LI) antibody response. Irradiated spleen cells and enriched specific B cells from HI and LI mice co‐isogenic at H‐2 s locus, were compared for their capacity to present chicken ovalbumin (OVA) to specific T‐cell hybridomas. Minor differences were observed between HI and LI mice when three distinct hybridomas were stimulated in the presence of OVA and splenic macrophages APC. These differences were totally abolished when APC were pulsed with OVAxAb complexes. Looking at the B‐cell compartment, hybridoma IL‐2 responses were similar when TNP primed B cells were pulsed with OVA. However, when OVA was targeted on TNP‐specific enriched B cells by pulsing with TNP‐OVA, the IL‐2 production by the T‐cell hybridomas was stronger in the presence of HI B cells than in the presence of LI B cells. These results strongly suggest that an efficient Ag handling/processing by specific B cells is a major component of the high Ab responder status in Biozzi mice.