Publisher Summary This chapter describes membrane immunoglobulins and antigen receptors on B and T lymphocytes. There are several qualitative and quantitative distinctions between T-cell and B-cell M-Ig that may explain many of the apparent differences in reactivity of these cells without requiring the existence of a different set of V genes or non-Ig receptors in T cells. Both T and B cells derive from hematopoietic, precursor, stem cells by antigen-independent differentiation. This involves the activation of L-chain and p-type H-chain genes in both cell types. The T-cell and B-cell M-Ig differ primarily in density per cell and possibly in relative exposure on the cell surface with much of the H-chain Fc region inaccessible on T cells. Moreover, the antigen-recognition receptor of both T and B cells involves their M-Ig. On B cells, the receptor is solely the M-Ig, whereas on T cells it is suggested that the specificity of recognition controlled primarily by the M-Ig and binding of antigen to the cell can solely be by the M-Ig receptor. Finally, the activation of the T cell requires an additional interaction of the antigen with another ceIl surface structure that is coded for by a polymorphic H-2 linked gene.

Membrane immunoglobulins and antigen receptors on B and T lymphocytes.

Germfree BALB/c mice have been treated from birth with intraperitoneal injections of purified goat antibodies to mouse IgM. The treated mice, and controls which had received an equivalent amount of goat γ-globulin, were sacrificed at 8 or 13 wk of age. Compared to controls, mice given anti-µ ( a ) had very few germinal centers in spleen and lymph node, ( b ) had decreased numbers of mature plasma cells synthesizing IgM and IgG1 in spleen, and virtual absence of IgA-synthesizing plasma cells in the gut, ( c ) had greatly diminished numbers of B lymphocytes bearing membrane-bound immunoglobulins of the IgM, IgG1, IgG2, and IgA classes in spleen, ( d ) had reduced synthesis of IgM, IgG2, and IgA by in vitro spleen cultures, and ( e ) had significant decreases in serum levels of IgM, IgG1, IgG2, and IgA. The treated animals failed to make antibodies to ferritin after hyperimmunization, and lacked natural antibodies to sheep erythrocytes. These results indicate that cells ultimately committed to synthesis of IgG1, IgG2, and IgA immunoglobulins are derived from cells which have expressed IgM determinants at an earlier stage of differentiation. They are consistent with a proposed two-stage model for plasma cell differentiation. The first stage is antigen independent, involves sequential activation of Cµ, Cγ, and Cα genes by progeny of a single stem cell, and results in the formation of B lymphocytes bearing membrane-bound recognition antibodies of each class. The second, antigen-dependent, stage results in formation of mature plasmacytes and memory cells.

/pdf/suppression-of-immunoglobulin-class-synthesis-in-mice-i-4n17f6aopu.pdf

SUPPRESSION OF IMMUNOGLOBULIN CLASS SYNTHESIS IN MICE I. EFFECTS OF TREATMENT WITH ANTIBODY TO µ-CHAIN

Previous experiments suggested that the spleen might not be the chief source of serum antibody synthesized several months after the immunization of mice by sheep erythrocytes; this has been confirmed for classes other than γM. The anatomical location of the cells making the antibody is not the same for each class. The thymus contains a relatively greater number of non-γM antibody-producing cells late in the response than it does in the first three weeks after immunization.

The long-term distribution of antibody-forming cells.

HLA-A, B, C and DR typing was performed in 19 patients with sarcoidosis of acute onset. Besides bilateral hilar lymph node enlargement (BHL), ankle joint involvement was found in all and erythema nodosum in seven. HLA-B8 was present in 13 and HLA-DR3 in 17 of the 19 patients. The joint manifestations and the erythema nodosum subsided in all within three months. The BHL regressed completely in seventeen patients during a three year observation period. In two patients with an observation period of one year and less than six months, respectively, BHL were still visible.



The strong association between the acute, prognostically beneficial manifestation of sarcoidosis and HLA-DR3 might partly be related to the presence of circulating immune complexes in acute sarcoidosis as well as to an immunogenetically determined handling of a postulated etiological antigen.

HLA-B8/DR3 in sarcoidosis. Correlation to acute onset disease with arthritis.

The discovery that in birds and mammals lymphoid cells mediating delayed sensitivity are developmentally and, in part, functionally independent from those involved in antibody production has greatly stimulated research on the cellular aspects of immunity. Recognition that B and T cells are separate populations has led to the definition of morphologic and functional markers for these cell lines. These markers have made it feasible to study the early events of lymphoid differentiation.

Modification of B Lymphocyte Differentiation by Anti-Immunoglobulins

Improvements have been made in a localized haemolysis in gel replica assay developed previously The technique is designed to show if an individual antibody producing cell releases antibody of one or more classes The techniques can also be used to indicate the specificity of antibodies produced by individual cells by using two different antigens in the test system In experiments where both slides of a slide-pair are untreated or treated identically, and 100% coincidence of plaques is expected, the technique has been shown to detect about 95% coincidence Pairs of slides treated differently to reveal plaques due to antibodies of different classes show a mean of about 3·5% coincident plaques This `background' of coincidence which it is thought is not due to `double-producers', is one of the limiting factors of the technique

Replica analysis of the class of antibodies produced by single cells.

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Replica analysis of the class of antibodies produced by single cells.