Strain A/J mice made secondary indirect plaque-forming cell (PFC) responses to azobenzenearsonate (ABA) conjugates of giant keyhole limpet hemocyanin (KLH), a thymic-dependent antigen, but not to conjugates of Ficoll, a T-independent antigen. ABA-Ficoll was also unable to elicit a response in animals primed with ABA-KLH, which have an expanded anti-ABA memory cell pool. On the other hand, ABA-Ficoll rendered mice unresponsive to ABA-KLH when administered before priming or boosting with the T-dependent immunogen. Hence, the T-independent antigen was able to tolerize but unable to trigger B-memory cells responsive to the T-dependent antigen. A/J mice immunized with dinitrophenyl conjugates of Ficoll or bovine IgG (BGG) made vigorous IgM and IgG PFC responses. PFC responses to ABA-KLH and 2,4-dinitrophenyl (DNP)-BGG were abrogated by depleting mice of C3 with cobra venom factor, whereas the IgM and IgG PFC responses to DNP-Ficoll were unaffected. B lymphocytes were fractionated on the basis of receptors for C3 and the subpopulations were assayed for in vitro PFC responses to DNP-Ficoll. Very little response was obtained from complement receptor lymphocyte [CRL(+)] B cells, whereas CRL(-) cells were more responsive than unfractionated B cells. Both populations responded to a polyclonal B-cell mitogen (lipopolysaccharide). On the other hand, the in vitro PFC response to a T-dependent antigen (sheep erythrocytes) correlated with the presence of CRL(+) B cells in the cultures. However, a minor component of this response, sensitive to anti-Thy-1 serum, was made by CRL(-) B cells, indicating the existence of subpopulations of T-dependent B cells with different signalling requirements. The results suggest that most B cells responsive to T-dependent antigens possess receptors for C3 and that C3 plays an obligatory role in the response of these cells. A distinct subpopulation of B cells which lack C3 receptors respond to T-independent antigens. The precursors of PFC for the ABA epitope reside largely or exclusively in the CRL(+) compartment in A/J mice, whereas precursors for the DNP determinant are found in both compartments.

Numerous antigens are now known that can induce antibodies bearing similar or identical variable region determinants (idiotypes) in all individuals of one or more strains of inbred mice (1-3). In many cases, the immune response to such antigens is of a highly restricted character, as judged by isoelectricfocusing (IEF) 1 of induced antibodies or other criteria. A curious feature is that the fraction of antibodies bearing a particular cross-reactive idiotype (Id) varies markedly between the known systems. Characteristic values indicating the extent of idiotypic dominance in the various systems can be tabulated (4). For example, ~30-35% of induced antibodies to group A streptococcal carbohydrate in A/J mice bear a common Id, designated A5A (5). In contrast, the response of BALB/c mice to the phosphorylcholine (PC) determinant, presented on T-independent (6) or T-dependent (7) carriers, is almost entirely (>--90%) dominated by antibodies bearing the T15 Id. Many of the factors that determine the extent of dominance of a paricular Id in a given response are obscure, although the clonal heterogeneity of B cells capable of responding to the epitope is likely to be important.The enumeration of characteristic values of clonal dominance implies a certain degree of stability. However, situations are known in which the representation of particular Ids changes considerably during the course of a response or during a multiple immunization regimen. MacDonald and Nisonoff (8) reported that crossreactive idiotypic specificities, present in the sera of individual rabbits early in the course of a hyperimmunization schedule with a p-azobenzoate conjugate, were replaced, at 2-4 mo, by a new set of cross-reactive specificities. A better-defined system, the NP-b Id present on anti-(4-hydroxy-3-nitrophenyl)-acetyl (NP) antibodies of C57BL/6 mice, has been analyzed by M~ikel~i and Karjalainen (9) and Jack et al.

Histocompatibility is necessary for many collaborative and aggressive cell interactions. The sharing of alleles at certain loci of the H-2 region on chromosome 17 of the mouse is essential for optimal interaction of lymphocytes with each other (1-7), with macrophages (8, 9), and with target cells in certain types of cytotoxic killing by T lymphocytes (10)(11)(12)(13)(14)(15)(16)(17). This evidence indicates that lymphocytes can and must recognize products of the H-2-chromosomal region for optimal responses to take place.Several curious observations which bear on the general question of self-recognition by lymphocytes have appeared in the recent literature. Koskimies and M~ikel~i (18) reported that T-cell-deficient mice made stronger anti-hapten responses to conjugates of syngeneic erythrocytes than to conjugates of allogeneic or xenogeneic erythrocytes. These findings, together with others demonstrating that an appreciable fraction of murine lymphocytes form rosettes with autologous, but not with isologous, erythrocytes (19)(20), support the existence on at least some immunocytes of a receptor for a self-marker which is expressed on erythrocytes.Because this form of self-recognition is likely to be of significance for a complete understanding of the mechanisms of lymphocyte activation, it was of interest to further investigate the phenomenon of autologous rosette formation. The present study confirms the phenomenon, establishes that the receptor in question is expressed on both T and B lymphocytes, and that it is not immunoglobulin in nature. Moreover, the use of recombinant strains of mice indicates that this form of self-recognition is associated with a marker coded by a new locus in the H-2-region mapping between H-2G and H-2D.

Thymus-derived lymphocytes exert a number of regulatory and effector activities in the immune system. Evidence has accumulated in recent years that these activities are largely executed by distinct subsets of T cells that can be distinguished by particular cell surface antigens (1, 2). This has led to the concept of a complex network of T cell types, each endowed with its own specific function. Rigorous proof of this concept has been difficult to achieve with heterogeneous cell populations. Recently, it has been possible to establish and maintain for prolonged periods in culture antigen-specific T cell lines (3, 4), paving the way to a more definitive approach to this question. Homogeneous populations of antigen-specific T cells should also prove extremely useful for studies of the chemical nature of the antigen in its activating form, as well as the nature of the T cell antigen receptor itself. In addition, comparison of these parameters between different functional subsets of T cells specific for the same antigenic determinant should be possible.We report here the establishment, genetic control, and preliminary characterization of the antigen specificity of normal T cell lines specifically responsive to a structurally defined epitope, L-tyrosine-p-azobenzenearsonate (ABA-Tyr)) It had been established previously (5, 6) that this simple synthetic compound is immunogenic in guinea pigs and mice. Accordingly, A/J mice were immunized with ABA-Tyr, and lymph node cells from the immune animals were used to establish antigen-reactive T cell lines. Strain A/J mice were chosen for this purpose because their anti-ABA antibody response is dominated by a major cross-reactive idiotype (7), providing the possibility of useful markers for the purification and characterization of T cell antigen-specific molecules as well as studies of the regulation of idiotype expression in antibody responses. The functional activity of these ABA-Tyr-specific T cell lines will be the subject of another communication.

In a series of pig brains submitted from field cases where water deprivation/sodium salt intoxication was suspected, histopathological examinations and chloride determinations were performed. A poor correlation was found between brain chloride concentration and neuropathology. The ranges of chloride concentrations found were similar for brains showing the encephalopathy of water deprivation/sodium salt intoxication, brains with other neuropathological diagnoses and brains without significant histopathological lesions. A close correlation was found between brain sodium and chloride in a further similar series, suggesting that determinations of sodium would not be more helpful diagnostically than determinations of chloride. A wide range of brain chloride values was also found in a group of healthy slaughtered pigs but the significance of this was not apparent. Brain chloride determinations have little value in the diagnosis of water deprivation/sodium salt intoxication in pigs, especially when performed in isolation without concurrent neuropathology and an adequate clinical history.