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B A Pollok

Publications and source records attributed to B A Pollok.

24 records · Page 2Linked to original sources
PubMed1984

Identification and characterization of an apparent germline set of auto-anti-idiotypic regulatory B lymphocytes.

By fusing BALB/c splenic lymphocytes from mice immunized with phosphorylcholine (PC) to an immunoglobulin nonproducing plasmacytoma cell line, a B cell hybridoma was isolated (MM-60) that has been shown by multiple criteria to produce a bona fide auto-anti-(anti-T15 idiotype) antibody. In vivo administration of MM-60 antibody suppressed T15+ anti-PC antibody production in an idiotope-specific manner by activation of an intervening set of anti-T15 B cells. These T15-specific B cells i) appeared to express germline-encoded variable region gene products, ii) developed in parallel to, but independent of, T15+ B cells, and iii) suppressed the anti-PC response in a T cell-independent fashion. Variants of T15+ anti-PC B cells possessing aberrant immunoglobulin heavy chain D region structure escaped from the suppression imposed by this anti-T15 B cell set, suggesting that a function of the heavy chain D region may be to contribute to the formation of molecular target sites for idiotype-directed regulatory cells and/or antibodies. The indigenous nature of these particular populations of anti-idiotypic and anti-(anti-idiotypic) B cells and the ability of their immunoglobulin products to regulate antigen-specific B cells in vivo provides strong supportive evidence for the significant role idiotype-directed network interactions play in regulating specific antibody production during a normal immune response.

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PubMed1983

Analysis of idiotypic heterogeneity in the anti-alpha 1-3 dextran and anti-phosphorylcholine responses using monoclonal anti-idiotype antibodies.

Panels of monoclonal anti-idiotype antibodies (MAIDs) specific for individual (IdI) and cross-reactive (IdX) idiotopes were prepared and used to study the expression of these idiotopes on anti-DEX and anti-PC antibodies produced in response to antigenic stimulation in vivo, clonal expression of idiotopes in an in vitro splenic focus assay, and the alterations in the idiotypic profile of these responses after in vivo administration of monoclonal anti-Id antibodies. Using these panels of MAIDs, it was possible to inactivate IdI-bearing B cells both in neonates and adult mice without affecting the responsiveness of IdI- B cells. By contrast, suppression with IdX-specific antibodies resulted in greatly reduced antibody responses. By studying the idiotypic profile of anti-DEX clones in the splenic focus assay, it was shown that IgM, IgG, and IgA antibody Id were diverse and paralleled those expressed in serum. Within some clones there was evidence that idiotope-isotype associations differed, suggesting that V region variants may have been generated within the progeny of a clone following stimulation by dextran. An anti-anti-Id antibody isolated from a BALB/c mouse undergoing a normal immune response to R36A was shown to have a T-cell independent highly idiotope-specific regulatory effect on the T15+ anti-PC response, apparently affecting induction of anti-idiotypic B cells.

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PubMed1981

Murine T cells that lyse antibody-sensitized target cells. III. Contribution of Thy 1-Bearing cells to the lytic activity of normal spleen.

Murine spleen cells were analysed for their capacity to lyse 51Cr-labelled antibody-sensitized erythrocytes and a human lymphoma cell line. Incubation of spleen cells with iron powder followed by removal of iron-containing cells with a magnet significantly decreased the lytic capacity of the remaining cells against erythrocyte target cells. However, substantial cytotoxicity remained in the relatively phagocyte-depleted population. Both antibody-sensitized erythrocytes and tumour cells were lysed by phagocyte-depleted effector cells. However, more spleen cells were required to lyse nucleated target cells than were required to produce comparable lysis of the erythrocytes. Such phagocyte-depleted spleen cells were subsequently treated with three different antisera containing specificities for thymus-dependent antigens and a monoclonal IgM anti-Thy 1.2 in the presence of complement. The remaining viable cells were recovered and tested as effector cells. All four reagents in the presence of complement caused an inhibition of antibody-dependent cell-mediated cytotoxicity (ADCC) that was proportional to the percentage of T cells eliminated. However, the antisera also inhibited ADCC in the absence of complement, even when the cells were trypsinized following the antiserum treatment to remove attached antibodies. On the other hand, treatment of spleen cells with the monoclonal IgM anti-Thy 1.2 followed by trypsin treatment did not inhibit ADCC unless complement was added. Thus, with the latter reagent, decreased ADCC could be ascribed to elimination of T cells and not immune complex inhibition. Cells bearing Thy 1.2 accounted for approximately half of the lytic activity of phagocyte-depleted spleen cells against antibody-sensitized target cells.

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PubMedDate not supplied

A biological consequence of variation in the site of D-JH gene rearrangement.

One mechanism which generates diversity in immunoglobulin variable (V) regions is flexibility in the site of recombination among the constituent genetic elements. Within a specific antibody family (that is, a particular VH-VL combination), variability in V-D-J rearrangement not only leads to sequence diversity at the boundary of the juxtaposed genes, but also enables the total length of the third complementarity-determining region (CDR-3) of the heavy chain to be conserved. We demonstrate here that the junctional diversity inherent in rearranged immunoglobulin genes can have consequences for the biology of the immune system. Sequence analysis of the expressed immunoglobulin genes of idiotypically variant as opposed to conventional B lymphocytes of a dominant antibody family showed that the variant B cells undergo a novel D-JH joining event such that an extra amino acid is inserted into the heavy chain CDR-3. The unique D-region conformation possessed by the variant B cells accounts for previous observations which showed that variant and conventional B cells could be differentially regulated in vivo by an autologous set of idiotope-specific B lymphocytes. Our findings indicate that D-region structure can determine the expression of regulatory idiotopes and suggest that the conservation of heavy-chain CDR-3 length within an antibody family may reflect regulatory as well as functional constraints.

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