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Biomedical subjects

B Rubin

Publications and source records attributed to B Rubin.

At least 127 records · Page 7Linked to original sources

On the molecular basis of T helper cell function. II. B-lymphocyte promotor factors: I-A-restricted production and their apparent antigen-independent, direct interaction with B cells.

The differentiation of Ig+ B cells into plaque-forming cells is dependent on antigen and factors produced by T cells and/or macrophages. We describe here the production of T-cell factors termed lymphocyte promotor factors (LPF). A foetal calf serum-specific T-cell line and its clones synthesize LPF, which is defined as factors that polyclonally stimulate normal spenic T cells to differentiate into cytotoxic T lymphocytes (T-LPF) and normal splenic B cells to differentiate into plaque-forming cells into (PFC) (B-LPF) in the apparent absence of specific antigen. The proliferation of and the B-LPF production of all T-cell clones tested were foetal calf serum-specific and I-Ab-restricted. Some of these clones produced only T-LPF, some clones produced only B-LPF, and some clones produced both T-LPF and B-LPF. B-LPF stimulate the polyclonal differentiation of Ig+ B cells into PFC without the apparent need for helper T cells, is different from T-LPF, and induces almost exclusively IgM PFC. The B-LPF described in the present paper are compared with previously described T-cell factors, which stimulate antigen-specific B-cell responses or bystander B-cell responses. The conclusion is that B-LPF are probably different from B-cell growth factors, T-cell replacing factors, allogeneic effector factors, and interleukin 2.

Animals↗

On the molecular basis of T helper cell function. III. B-lymphocyte promotor factors: production by T hybridoma and tumour cells; preliminary biochemical characterization.

B-lymphocyte promotor factors (B-LPF) are defined as T-cell-derived, released molecules that trigger polyclonal induction of B-cell differentiation into antibody-forming cells. B-LPF activity is independent of antigen, and it apparently induces only IgM-producing B cells. B-LPF was discovered as products of an antigen-specific, I-Ab-restricted T-cell line. We here show that B-LPF is produced also by lymphoma cells derived from this T-cell line or by T-cell hybrids constructed by fusing the T-cell line with BW5147 thymoma cells. A chicken gamma globulin-specific T-cell hybridoma clone also produced B-LPF. Biological assays demonstrated that B-LPF-containing supernatants did not contain IL-1, IL-2, B-cell growth factor, or allogeneic effector factor. Biochemical studies showed that B-LPF was precipitated by 50% (NH4)2SO4 saturation and that at least three types of molecules were involved in B-LPF activity: molecules with molecular weights of greater than 90,000, 50,000-90,000 and 10,000-25,000. The relationship between B-LPF and antigen-specific helper/inducer factors is discussed.

Animals↗

Percutaneous transrenal balloon dilatation of the ureter.

Six strictures of the ureter were dilated with balloon angioplasty catheters. Two obstructed ureterovesical junctions in transplant patients were successfully treated. One obstructed ureteropelvic junction in a transplant kidney with a redundant ureter failed to respond. One of 2 uretero-ileostomy junction strictures was successfully treated, though one mid-ureteral stricture remained unchanged. Multiple dilatations were necessary in several patients. No significant complications were noted. Pre- and post-dilatation assessment of obstruction using the Whitaker test was helpful in transplant patients.

Adult↗

Idiotypes and allotypes on Ia-binding alloactivated Lyt-1+,2-,3- T cells are coded for by genes linked to the igh-1 allotype locus.

Xenogeneic antisera, designated 5936 and 6036, have been used in this laboratory to define 5936-idiotypes (Id) and 6036-T cell receptor (Tcr) allotype determinants, respectively, on populations of B6 anti-CBA MLC T blasts. The present experiments were carried out to determine a) whether T lymphocytes that bear 5936-Id also express antiserum 6036-defined Tcr allotypes; b) if so, what is the Lyt phenotype and c) specificity of this T lymphocyte population, and d) whether the genes coding for 5936-Id and 6036-allotypes are linked to immunoglobulin (Ig) allotype genes. The results showed that 5936-Id-bearing T lymphocytes were included in a subset of cells that expressed antiserum 6036-defined Tcr allotypic determinants and the Lyt-1+,2-,3- phenotype. By genetic segregation analysis it was shown that both 5936-Id and antiserum 6036-defined allotypic determinants on T cells were linked to Igh-1b allotypes. 5936-Id determinants were expressed on T lymphocytes of Igh-1b allotype strains, specific for allogeneic I-Ak but not on those specific for I-Ak/Ek molecules. In contrast, 6036-Tcr allotype determinants were present on T lymphocytes from Igh-1b allotype strains, specific for either I-Ak or I-Ak/Ek molecules. The results support the hypothesis that 5936-Id determinants are present only on a subset of anti-I-Ak T cell receptors, whereas 6036-Tcr allotype determinants are shared among T cell receptors of several unrelated specificities from Igh-1b allotype-bearing strains.

Animals↗

Crystallization and preliminary x-ray data for a glycosylated form of bovine pancreatic ribonuclease.

A glycosylated form of bovine pancreatic ribonuclease, ribonuclease B, has been crystallized in a form suitable for three-dimensional x-ray structure determination. Crystals grown from polyethylene glycol solutions display high resolution diffraction patterns indicating the orthorhombic space group P2(1)2(1)2(1) with a = 59.2 (+/- 0.1), b = 56.0 (+/- 0.1), and c = 81.0 (+/- 0.2). A, V = 2.7 x 10(5) A3. With 8 molecules/unit cell Vm = 2.28 A3/dalton. The systemically weak intensity of all reflections with their l indices odd suggests the likely alignment of a noncrystallographic 2-fold axis near the crystal c axis.

Animals↗

Crystallization and preliminary X-ray data for chloroperoxidase.

The enzyme chloroperoxidase from the fungus Caldariomyces fumago has been crystallized in a form suitable for detailed three-dimensional x-ray structure determination. Crystals grown from polyethylene glycol solutions display high resolution diffraction patterns indicating the orthorhombic space group C2221: a = 151.1 (3), b = 57.9 (4), c = 102.7 (9) A, V = 9 X 10(5) A3. A volume to mass ratio Vm = 2.8 A3/dalton for 8 molecules in the unit cell and a measured density of 1.35 g/cm3 suggest that the asymmetric unit contains a single chloroperoxidase molecule.

Animals↗

T cell idiotypes recognizing self-major histocompatibility complex molecules: H-2 specificity, allotype linkage, and expression on functional T cell populations.

An anti-idiotypic serum (antiserum 5936, B. Rubin et al., J. Exp. Med. 1979. 150: 307) was used to demonstrate receptor sites for self-major histocompatibility complex (MHC) antigens on T lymphocytes. The antiserum was raised by injecting rabbits tolerant to mouse Ig with a B6 anti-CBA (anti-H2k) alloantibody. It recognized a large proportion of T cells from H-2k strains carrying the b, c, d or e allele at the Igh-1 locus, but only a few T cells from H-2k strains with Igh-1 alleles a, f and j. Allotype linkage of the 5936 idiotype was also demonstrated by segregation analysis. The antiserum did not recognize either H-2k B cells or T cells from other H-2 haplotypes despite the presence of a permissive Igh-1 allele. The 5936 idiotype was found to be associated with several different antigen specificities, indicating that it is not located on the binding site for foreign antigen. Furthermore, the 5936 antiserum inhibited the binding of soluble Ik antigens by H-2k, Igh-1b, T cells, and, in the presence of complement, eliminated T cells responding to different antigens in an I-Ak-restricted fashion. Collectively, the data indicate that the structure bearing the 5936 idiotype is a receptor for I-Ak antigens, expressed by strains carrying the I-Ak allele and a permissive allele at the Igh-1 locus. The relevance of this finding to the MHC-restricted recognition of antigens by T cells is discussed.

Animals↗

Genetic chasing of T helper cell idiotype and allotype genes.

The present experiments were performed to study whether the genes responsible for the expression of T-idiotypes and allotypes could be mapped in relation to immunoglobulin (Ig) heavy chain V- and C-genes. Use was made of our antiserum 5936, which detects idiotypes in B6 and anti-B10.BR sera and on Lyt-1+, 2.3-B6 anti-B10.BR T-cell populations, and antiserum 6036, which detects allotypes on Lyt-1+, 2.3-B6 T cells, but which does not react against Ig. The reactivity of these antisera with T cells from (B6 X C3H.OH) X C3H.OH backcross mice and CBA-allotype congenic B6 mice was investigated because 5936 idiotypes and 6036 allotypes appeared to be associated with Igh-1b genes (B6) and not with Igh-1j genes (C3H.OH,CBA). Our results will show, first, that 5936 idiotypes on Lyt-1+, s.3-B6 anti-B10.BR T cells are synthesized by genes linked to Igh-1b allotype genes and they are situated either within Ig heavy chain V-genes or centromeric to them. Second, our results will show that 6036 allotypes on Lyt-1+, 2.3-B6 T cells are produced by genes also linked to Igh-1b-allotype genes, and the 6036 allotype genes are situated between Ig-VH and prealbumin genes.

Absorption↗

Rigid compression screw fixation of first proximal phalanx osteotomy for hallux abducto valgus.

Various external and internal immobilization techniques have been employed when performing a medial closing wedge osteotomy at the first proximal phalangeal base for the correction of hallux abducto valgus. Internally, the techniques used such materials as absorbable and nonabsorbable suture, monofilament stainless steel wire, osteoclasps, ministaples, and Kirschner wires. In this study, we have employed the A.O.3 technique of rigid compression screw fixation across the osteotomy site. Three different types of screws were utilized; 3.5-mm. and 4-mm. Bechtol screws and 2.7-mm. cortical bone screw, all of which were 3 cm. in length. Eight procedures were performed for six patients. The authors found the benefits afforded by rigid fixation according to the A.O. technique with respect to the production of postoperative callus at the osteotomy site to be superior in comparison to other modalities of fixation.

Adult↗

Idiotypic regulation of mouse anti-H-2 antibody responses. I. induction of 5936-idiotype-bearing Ig molecules upon immunization with H-2k alloantigen.

Mouse-immunoglobulin (MIg) tolerant rabbits immunized with mouse H-2 antibodies produced anti-idiotype antisera, which were reactive towards specific B- and T-cell receptors. One such rabbit antiserum (from rabbit 5936) defines a family of idiotypes (Id) designated 5936-idiotypes (Rubin et al. 1979). The present experiments were performed in order to establish (1) the nature of 5936-Id+ serum molecules, (2) the specificity of 5936-Id+ serum molecules, (3) the association of the 5936-Id genes to allotype and/or H-2 genes and (4) the immunological role of 5936-Id+ serum molecules. A sensitive radioimmunoassay employing 125I-labelled-F(ab)2 fragments of B6 anti-B10.BR MIg pool, 5936 antiserum, and a sheep anti-rabbit immunoglobulin antiserum, was used.--The results suggested that 5936-Id+ serum molecules were exclusively MIg, and that they were mainly of the IgG1 class. Such molecules were induced in B6 mice (H-2b/Ig-1b) upon immunization with H-2k but not with H-2q alloantigen or conventional antigens. The 5936-Id were found to be associated with Ig-1b allotypes and the H-2b complex may contain immune response (Ir) genes which, in comparison with Ir genes in H-2d and H-2s, favor the expression of 5936-Id.--Adsorption of 5936-Id+ B6 anti-CBA MIg preparations on CBA (IAk) spleen cells demonstrated that CBA antibodies were 5936-Id-. It is discussed whether 5936-Id+, IgG1 molecules in B6 anti-CBA sera are anti-(anti-CBA) antibodies or nonspecific antibodies, the production of which is augmented by immunization with IAk alloantigen.

Absorption↗

Rabbit antisera with specificity for isolated mouse T-lymphocyte receptors.

Rabbit antibodies obtained after immunization of mouse immunoglobulin (MIg)-tolerant rabbits with B6 anti-CBA IgG and having specificity for B6 anti-CBA IgG and T-cell receptors (antiserum 5936) were used to isolate 5936-reactive molecules from B6 anti-CBA mixed lymphocyte culture supernatants. Such 5936-reactive molecules were produced by the B6 T cells, and they did not react with rabbit anti-MIg antisera. They had a mol. wt of 50,000-75,000, and were single-chain polypeptides that did not react with concanavalin A (Con A)--Sepharose. These molecules were in turn injected into rabbits, and the antisera thus obtained had the following characteristics: (1) they reacted against B6 anti-CBA T-cell receptor material but not against B6 anti-CBA IgG; (2) they reacted with about 35% of B6 (H-2b, Ig-1b) anti-CBA T cells, 25% of B6 Con A blasts and 0-10% of normal B6 T cells but not with B6 lipopolysaccharide (LPS) blasts, C3H.B10 (H-2b, Ig-1j) anti-CBA or CBA anti-B6 T cells, CBA Con A blasts or normal CBA T cells; and (3) they reacted with the same 50,000-75,000 mol. wt, T-cell-derived molecules as did antiserum 5936. The implications of these findings are discussed in relation to the nature of T-cell receptors.

Agglutinins↗

The 5936 Ig-idiotype(s): genetic linkage to Ig-Ch Loci, T-cell dependence of synthesis and possible specificities.

5936-idiotype(s) are defined by a rabbit antiserum which was obtained by immunizing a mouse-immunoglobulin(MIg)-tolerant rabbit 5936 with B6 anti-CBA Ig from a single B6 mouse. These idiotypes were found on IgG1 molecules in sera from B6 mice immunized with cells carrying the IAk alloantigen, and they were associated with B6 Ig allotypes (Igh-1b). The particular interest of this idiotypic system is that antiserum 5936 also detects idiotypes (Id) on B6-T cells immunized in vitro with IAk alloantigen, and such T-cell Id were found to be associated with Ig allotypes. We attempted to show that the 5936-Id on Ig molecules were linked to Igh-1b allotypes by backcross analysis. In addition, it was investigated whether the 5936-Id response was a T-cell dependent response, and, if so whether there was any restriction in this T-B cell collaboration. Finally, we continued our studies on the specificity of 5936-Id+ Ig molecules. The present experiments show that 5936-Id are linked to Igh-1b allotypes and that the quantity of 5936-Id produced appears to be regulated by Ir genes in the H-2 complex. The synthesis of 5936-Id is T-cell dependent, and only Igh-1b allotype compatible T cells would collaborate with 5936-Id+ B-cell precursors. 5936-Id+ Ig molecules appeared not to have specificity against eco- and xeno-tropic viruses. However, monoclonal antibodies produced from B6-T-cell-reconstituted B6 nude mice may carry 5936-Id and have specificity for B6-T-cell membrane molecules. The relevance of these findings to the question of whether or not T and B cells display identical idiotypes are discussed.

Animals↗

Analysis of a fetal calf serum-induced T cell line. I. H-2 restricted growth and expression of membrane-bound and released molecules bearing 5936-idiotypic determinants.

It was previously established that a fetal calf serum-induced C57BL/6 T cell line that induces T and B cell differentiation could be kept proliferating in vitro only if cultured in the presence of irradiated syngeneic spleen cells and FCS. The present experiments were performed in order to investigate a) whether this cell line was a pure T cell line, b) whether the cells in this cell line (called line 12) were homogeneous with regard to Lyt phenotype, c) whether its growth was H-2 restricted, and d) whether line 12 cells reacted with our anti-idiotype (5936) and anti-T cell receptor allotype/isotype (6036) antisera. The results showed that line 12 consisted of T cells of Lyt 1+, 2.3- and phenotype. Its growth and proliferation was restricted to Kb and/or IAb alloantigen, and this phenomenon was observed with isolated Lyt 1+, 2.3- T cells. Line 12 cells reacted with both 5936 and 6036 antisera, and the positive cells were of Lyt 1+, 2.3- phenotype. Thus, our data indicate that Lyt 1+, 2.3- line 12 T cells interact with FCS and Kb/IAb alloantigen via receptors, which may bear 5936 and 6036 antisera-defined determinants. However, because these antisera only react with a subpopulation of Lyt 1+, 2.3- cells, proof that the same T cell has both MHC specificity and B cell idiotypic determinants will require further experimentation. 5936 and 6036 antisera-reactive molecules could be isolated from the supernatants of line 12 cells. Such molecules had characteristics similar to the 50,000 m.w. form of receptor molecules isolated from B6 anti-CBA T cell supernatants: a single chain polypeptide carrying both 5936 and 6036 antisera-defined determinants.

Animals↗