Mitogen-reactive B cell subpopulations selectively express different sets of V regions.

Abstract

Polyclonal B cell activators (PBA) 1 are substances that directly activate B cells to clonal growth and antibody secretion by interacting with nonclonally distributed receptors on the surface of lymphocytes (1-5). The capability of B cells to respond to various PBA divides the B cell pool into different functional subsets that might or might not overlap with each other (6-9). Because polyclonal activation does not involve the variable region of immunoglobulin, the triggering is not immunologically specific, and, therefore, it has been proposed (6, 10) that the repertoire of antibody specificity is randomly distributed or even repeated among the "subsets" of B cell clones defined by reactivity to different mitogens. This proposal has been experimentally confirmed by observing increased antibody synthesis specific for conventional antigens or haptens induced by various PBA. These studies, however, did not take into account the extreme degeneracy of the immune system or, in other words, the great lack of precision in the fit betwen antibodies and antigens that can vary over a range of several orders of magnitude. Consequently, because of the extreme heterogeneity of the immune response, the question of whether different B cell subpopulations, as defined by mitogen reactivity, selectively express identical clonotypes has not been answered as yet. We decided to address ourselves to this question by comparing the expression of four idiotopes in spleen cells of BALB/c mice activated by two mitogens that have been described as acting on separate B cell subsets, i.e., lipopolysaccharide (LPS) and Nocardia delipidated cell mitogen (NDCM) (11).The 66, 137, and 395 idiotopes 2 are defined by BALB/c monoclonal antibodies against the monoclonal immunoglobulin (Ig) 174 to/~galactosidase produced by a BALB/c mouse. 3 None of these three determinants are normally expressed when BALB/c mice are immunized with flgalactosidase, and therefore they can be classified as nonrecurrent idiotopes. 3 Contrary to this, the M-460 idiotype (Id) specificity defined by the monoclonal anti-M460 antibody F6(51) is present on a portion of antitrinitrophenyl (TNP) antibodies produced by BALB/c mice after immunization with thymus-dependent or thymus-independent TNP antigens (12).We therefore determined the approximate frequencies of LPS-and NDCM-sensitive B lymphocytes secreting Ig molecules that bear the 66, 137,395, and M-460 idiotopes.

Regulation of Ig Class Secretion by Soluble Products of Certain T‐Cell Lines

“…For example, thymus independent antigens in vivo or in vitro give rise to IgG antibodies mainly of the IgG} subclass (Perlmutter et al 1978, Slack et al 1980, Izui et al 1981, whereas thymus-dependent antigens give IgGi and IgG2 antibodies (Perlmutter et al 1978, Slack et al 1980). Furthermore, "thymus independent" poiyclonal activation using lipopoiysaccharide (LPS) (Kearney 1979, Severinson Gronowicz et al 1979, Nocardia delipidated cell mitogen (NDCM) (Primi et al 1982), bacterial lipoprotin (LP) (Augustin & Coutinho 1980), a polyclona! activator from Actinomyces viscosus (Avis) (Clagett et al 1980), or RU 41.740 (Biostim) which is a glycoprotein extract from Klebsiella pneumoniae (Wood & Moller 1984), give, in addition to IgM, mainly IgG3 and IgG2b secretion.…”

Differential expression of sets of highly homologous variable region gene products in selected and preimmune repertoires of inbred mouse strains.

“…The usual characterization of preimmune B cell repertoire involves the analysis of antibodies secreted by mitogenically stimulated B cells. Although it may be questioned whether the complete repertoire of antibody specificities is present among mitogen-reactive B cell subsets (26)(27)(28)(29)(30), this methodology re- Frequencies determined as described in Materials and Methods. Absolute frequencies were determined by dividing the observed frequencies by the frequencies of LPS-sensitive cells.…”

The relationship between variable region determinants and antigen specificity on mitogen reactive B cell subsets.

“…The hemagglutination (HA) assay for idiotopes and antigen specificity detection was the method of choice, as we previously demonstrated (1) that this assay can detect at least 0.1 ng of ligand. The specificity of the assay has been previously described (1).…”