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J Couderc

Publications and source records attributed to J Couderc.

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[Heterogeneity of antibodies produced by individual cells].

Recent experimental findings indicate that individual B cells can produce simultaneously heterogeneous Ig molecules. Three orders of heterogeneity have been described. (1) In two published cases of human myeloma, individual malignant cells produced Igkappa and Iglambda (case Im) or IgMlambda and IgGkappa (case Br). (2) Immunofluorescence studies repeatedly showed that normal B cells may bear surface Ig of two different classes or cytoplasmic Ig of one class and surface Ig of another class. However, simultaneous production of two different CH chains by immunized B cells or myeloma cells appeared to be rather rare (1-3%). (3) Immunization of mice with two different antigens regularly results in the appearance of cells (1-3%) simultaneously reacting with both antigens. Specific inhibition of the one activity does not interfere with the other. Furthermore, bispecific cells cultured individually generate daughter cells, each producing antibody of only the one or the other specificity. It can be inferred from these findings that early B lymphocytes are pluripotential and that differentiation involves a process of phenotypical restriction directing the cell (plasma cell) to produce high quantities of one type of Ig molecule.

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Evidence for multipotentiality of antibody synthesizing cells.

Immunization of mice with two unrelated antigens or antigenic determinants regularly results in the appearance of hemolytic plaque forming cells (PFC) of each specificity and of some PFC (1-4%) reacting to both determinants. Micromanipulation of individual double PFC appearing after immunization with trinitrophenyl conjugated sheep erythrocytes (TNP-SRBC) into media containing indicator erythrocytes (native SRBC and TNP-horse RBC) and a soluble specific inhibitor (TNP-BSA or soluble SRBC antigen), showed that the specific inhibitor suppressed the lysis of the corresponding indicator but did not interfered with the lysis of the unrelated indicator. Persistance of one specific activity in spite of complete inhibition of the other indicated that these double PFC synthesize two different antibody molecules. The destiny of double cells was studied in individual cell cultures by micromanipulating them into wells containing heavily irradiated normal mouse spleen cells and both determinants (TNP-SRBC). Those double cells which divided they generated in 24 hours monospecific daughter PFC (either anti-TNP or anti-native SRBC). Individually cultured monospecific PFC from mice immunized with one antigen (native SRBC) generated daughter PFC of the same specificity. By contrast, monospecific PFC from mice immunized with TNP-SRBC generated PFC of either the same specificity of (more frequently) of the one the other specificity. Thus, immunization with substituted erythrocytes resulted in the development of three clonotypes: two clones each composed only of cells of either specificity (amphispecific clonotype). For the maintenance of this amphispecific clone, continuous presence in the culture media of both antigenic determinants was necessary. Removal of the one for 48 hours (but not for 24 hours) abolished the generation of daughter cells of the same specificity.

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