Demonstration of Heavy and Light Chain Antigenic Determinants on the Cell-Bound Receptor for Antigen

The influence of immunization with (T,G)-A--L on the frequency and characteristics of [125I] (T,G)-A--L-binding cells (ABC) was investigated in high and low responder mice, whose ability to respond to (T,G)-A--L is under control of an H-2-linked immune response gene, Ir-1. Unimmunized high and low responder mice have about the same number of ABC in spleen and lymph nodes (6–12 ABC/104). However, after immunization with (T,G)-A--L in aqueous solution, ABC in high responders increase to a much greater extent than they do in low responders. By inhibition of ABC with class-specific anti-Ig sera, it was demonstrated that in nonimmune and primed mice antigen is bound to IgM receptors, which is in agreement with the exclusive production of 19S anti-(T,G)-A--L antibody in primed animals. In contrast, after secondary challenge with antigen, ABC in high and low responder mice have mainly IgG receptors, although under the conditions used for immunization, low responders are not able to produce detectable amounts of 7S anti-(T,G)-A--L antibody. From these results and from the evidence that low responders very probably have a T cell defect, it is suggested that the switchover from IgM to IgG precursor cells can be induced by antigen itself, without the action of specific T cells. Furthermore, the failure of marked proliferation of ABC in low responders after antigenic stimulation is explained by the lack of stimulation by specific T cells. By independent methods it has been shown that all ABC detected in this study are B cells. Preliminary experiments indicate that purified peripheral T cells bind antigen, but much less per cell than do B cells.

Section: Discussionsupporting

confidence: 81%

Genetic Control of the Immune Response

Hämmerling

Masuda

McDevitt

1973

“…Anti-DNP antibody-secreting cells are bound by DNP-agarose conjugates equally well whether GPA or BSA is the protein carrier (6) and it has been shown that anti-Ig inhibits binding of antibody-secreting cells to antigen-glass bead columns (16). Thus, ABC and antibody-secreting cells appear to have similar surface receptors and these receptors resemble circulating antibody molecules in that they are immunoglobulins, they are hapten specific, and an avidity increase occurs in the course of the immune response.…”

Section: Discussionmentioning

confidence: 99%

Receptors on Immunocompetent Cells

Davie

Rosenthal

Paul

1971

Guinea pigs immunized with 2,4-dinitrophenyl-guinea pig albumin (DNP-GPA) possess lymphocytes which specifically bind sufficient DNP-GPA-125I to their surface to be detected by radioautography. These lymphocytes are present in the draining lymph nodes in a frequency of ∼50/1000 lymphocytes in animals immunized 2–4 wk earlier with DNP-GPA in complete Freund's adjuvant. Nonimmunized animals have ∼0.4 DNP-GPA antigen-binding cells (ABC) per 1000 lymphocytes. An increase in the frequency of DNP-GPA ABC in peripheral blood is detectable by 5 days after immunization, which is before the time that serum anti-DNP antibody is measurable. The receptors of these ABC are hapten specific in that free ϵ-DNP-L-lysine, at low concentration, inhibits the binding of DNP-GPA-125I; DNP bovine serum alumbin (DNP-BSA) is equivalent to DNP-GPA in the inhibition of binding of DNP-GPA-125I to ABC; and both DNP-GPA agarose beads and DNP-BSA agarose beads specifically adsorb DNP-GPA-125I ABC. Anti-immunoglobulin antisera, particularly anti-γ2 sera, inhibit the binding of DNP-GPA-125I to these cells implying that the receptors are immunoglobulin, primarily of the γ2 heavy chain class. DNP-GPA-125I ABC appear to represent precursors of antibody-secreting cells and have specificity characteristics which are very different from cells, of similarly immunized guinea pigs, which mediate a cellular immune response to DNP-GPA.

“…By hypothesis, the specific combination of antigen with its receptor(s) results in activation of immune differentiation and subsequent synthesis of antibody, although under certain conditions specific inactivation and tolerance can ensue (1,2). Antigen receptors located on the surface of certain lymphoid cells (3)(4)(5)(6)(7)(8)(9) are considered to be representative of the eventual cell product with regard to both specificity and immunoglobulin class (10)(11)(12)(13). Therefore, the use of antibody directed against a particular class of heavy chain determinants displayed by antigen receptors could conceivably lead to the selective inhibition of the production of that immunoglobulin class resulting in an experimental dysgammaglobulinemia.…”

Section: (From the Department Of Immunology Mayo Medical School Rocmentioning

confidence: 99%

PRODUCTION OF a RUNTING SYNDROME AND SELECTIVE ΓA DEFICIENCY IN MICE BY THE ADMINISTRATION OF ANTI-HEAVY CHAIN ANTISERA

Murgita¹,

Mattioli²,

Tomasi³

1973

Conventional Swiss mice were treated from birth with intraperitoneal injections of anti-immunoglobulins in an attempt to create an experimental dysgammaglobulinemia. Mice treated with anti-γM were immunologically suppressed in all immunoglobulin classes as determined by serum antibody titers, splenic plaque-forming cells, serum immunoglobulin levels, and immunofluorescent analysis of plasma cells in lymphoid tissues. Treatment immediately after birth with high concentrations of anti-γM leads to a developmental arrest characterized by severe immunosuppression, failure to gain weight, and premature death. The pathogenesis of anti-γM runting syndrome is unknown. Animals similarly treated with anti-γG, anti-γA, or control normal goat or rabbit γ-globulins developed normally. The frequency of occurrence and severity of anti-γM-induced runting syndrome is dependent upon the concentration of anti-γM-globulin administered. Administration of anti-γA resulted in a selective γA deficiency that was characterized by a marked reduction in serum-γA and an absence of γA-containing cells in the spleen. However, essentially normal numbers of plasma cells were found in the gastrointestinal lamina propria of anti-γA-treated animals concomitantly with suppressed levels of γA in intestinal fluids.