Idiotypic restrictions are demonstrated in vitro for the cooperation between T and B lymphocytes with specificity for Group A streptococcal carbohydrate. T helper cells which have been primed in vivo with anti-idiotypic antibodies to the A5A idiotype and which are therefore essentially A5A idiotype-positive, cooperate only with A5A idiotype-positive B cells, even when mixtures of A5A idiotype-positive and A5A idiotype-negative B cells are present. Essentially A5A idiotype-negative T helper cells that have been primed in vivo with Group A streptococcal vaccine after in vivo suppression with anti-A5A idiotypic antibody are unable to cooperate with B cells which have been primed with anti-A5A idiotype antibody and which are therefore essentially A5A idiotype-positive. Mixtures of A5A idiotype-negative and A5A idiotype-positive T cells cooperate with both A5A idiotype-negative and A5A idiotype-positive B cells. Idiotypic restrictions could not be demonstrated for T and B cells recognizing carrier and hapten determinants, respectively, in experiments in which the cooperation of genetically VH-identical T and B cells was compared to the cooperation of genetically VH-different T and B cells. The data are discussed with respect to various models for the communication between T and B cells. It is proposed that for successful T-B cooperation, ordinarily two types of T helper cells are required, one recognizing the antigen and the other recognizing the idiotype of the B cell.
Unresponsiveness of strain A/J mice to sensitization with guinea pig IgG anti‐A5A idiotypic antibody is induced by prior injection of guinea pig IgG2 anti‐A5A idiotypic antibody or unfractionated anti‐A5A antiserum. Two different forms of unresponsiveness could be induced depending on the dose of IgG2 anti‐A5A: high‐zone suppression was maximal one week after injection, could not be transferred by lymphocytes and disappeared within 3 to 4 weeks. Low‐zone suppression took 7 weeks to fully develop and could be transferred by splenic and lymph node T cells.
High‐zone suppression is expressed as transient unresponsiveness in both the A5A‐idiotype‐positive T helper as well as B precursor cell compartments. Low‐zone, suppressor cell‐mediated suppression is expressed as chronic unresponsiveness in the A5A‐idiotype‐positive T helper cell compartment only, whereas the A5A‐idiotype‐positive B precursor cells remain fully responsive as revealed by addition of nonsuppressed T helper cells. These data satisfactorily explain that suppression of T helper cell‐independent idiotypes does not involve T suppressor cells. However, since the presence of suppressor T cells is accompanied by selective unresponsiveness of A5A‐positive B cells, the data imply that idiotypic restrictions exist for T‐B cooperation.
Antibodies to framework determinants of the VH and V lambda fragments of MOPC 315 and antisera to the VH idiotype determinants of the A 5 A antibody were used to analyze the antigen receptors of mouse T (and B) cells. This was done by using the antibodies as inhibitors in (a) an assay in which the binding of radiolabeled streptococcal carbohydrate (A-CHO) antigen by primed and unprimed T and B cells is determined and (b) an assay in which the helper activity of group A streptococcal vaccine-primed T cells is determined. The results suggest that the major proportion of primed and unprimed T cells binding A-CHO (70-90%) exhibit VH framework and VH idiotypic determinants. This population appears to include the helper T cells. A minor proportion of T cells (10-30%) express V lambda-related framework determinants and lack VH framework and VH idiotypic determinants. This population does not include T helper cells. Taken together, the data suggest that a subpopulation of T cells, including the helper cells, uses entire Ig VH regions as part of their antigen receptor system.
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