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Biomedical subjects

B S Kwon

Publications and source records attributed to B S Kwon.

At least 55 records · Page 3Linked to original sources
PubMed1997

Signals through 4-1BB are costimulatory to previously activated splenic T cells and inhibit activation-induced cell death.

Previously, we and others showed that signals relayed through the murine T cell Ag 4-1BB enhance primary T cell responses, and that blocking the interaction of 4-1BB with its ligand results in decreased responses to polyclonal activators and to alloantigens. Because 4-1BB expression is induced following primary stimulation, we investigated the role of signaling through this molecule in the reactivation of proliferating T cells. To this end, preactivated, 4-1BB-expressing T cells were restimulated in the presence of plate-immobilized mAbs directed against 4-1BB or the prototypic costimulatory molecule CD28. In this work, we show that in the presence of either signal, T cells respond to TCR cross-linking with strong proliferative responses and cytokine production; moreover, our findings indicate that T cell proliferation partially correlates with surface 4-1BB expression. In addition, our results suggest that Ab-mediated costimulatory signals can act independently of potential accessory B7-CD28/CTLA-4 (cytotoxic T lymphocyte Ag-4) interactions. Importantly, the characteristic DNA fragmentation and apoptotic cell death observed after TCR re-engagement are inhibited comparably in the presence of either 4-1BB or CD28 signaling.

Animals↗
PubMed1996

A critical role of Sp1- and Ets-related transcription factors in maintaining CTL-specific expression of the mouse perforin gene.

This study was designed to determine the potential cis-elements involved in transcriptional regulation of the mouse perforin gene. DNase I hypersensitive site (DHS) mapping revealed that the perforin locus contained six DHS within 7.0 kb of the 5' upstream sequence (-7.0 kb) and two DHS in intron 2. The six 5' upstream and one intronic DHS were detected in only perforin-expressing lymphocytes. Chloramphenicol acetyltransferase (CAT) activities directed by 5' upstream promoter were detected preferentially in perforin-expressing cell lines. A construct termed PFP5a containing -795 bp exhibited the highest CAT activity, and PFP9a20 containing only -73 bp also produced significantly high CAT activity in CTLL-R8 cells. The proximal region in PFP9a20 contained two potential Sp1 binding sites (GC box and GT box) and one Ets binding site (EBS). Electrophoretic mobility shift assay showed that each of the cis-elements bound specific protein factors. When single-point mutation was introduced to each GC box, EBS, and GT box in PFP9a20, at least 3-fold less CAT activity was observed in CTLL-R8 cells. To confirm the importance of the three cis-acting elements in the perforin gene expression, point mutation was introduced again to each proximal GC box, EBS, and GT box of PFP5a. The point mutations resulted in a 2.5- to 3-fold reduction of CAT activity. The results suggest that a combination of the three proximal cis-acting elements may constitute a minimal region responsible for CTL-specific expression of perforin.

Animals↗
PubMed1996

4-1BB is expressed on CD45RAhiROhi transitional T cell in humans.

Murine 4-1BB is an approximately 30-kDa glycoprotein expressed on activated T cells and plays a role in T-cell-mediated proliferative response. To date the majority of work on 4-1BB has been conducted in the mouse. To assess the role of 4-1BB in humans, mAbs were made against the recombinant human (rh) 4-1BB protein. One such mAb 4B4-1 specifically binds SF-21 insect cells expressing rh4-1BB but not irrelevant control protein as measured by flow cytometry (FCM). 4B4-1 mAb stains PMA- and ionomycin-stimulated CEM (human T lymphoma) cells and PHA-stimulated peripheral blood T cells, but not resting cells. 4B4-1 mAb immunoprecipitates both approximately 32 and approximately 80 kDa protein from rh4-1BB expressing SF-21 cells and an approximately 39- and approximately 85-kDa protein from PMA-stimulated CEM cells under reducing conditions by SDS-PAGE. As added proof of its specificity, binding of FITC-labeled 4B4-1 mAb to PHA-stimulated T cells was blocked by rh4-1BB protein. Together these data demonstrate that 4B4-1 is specific for 4-1BB in humans. Unlike in the mouse, 4-1BB is expressed much earlier (within 24 hr) peaking around 2-3 days following PHA stimulation. As in the mouse 4-1BB is induced on both CD4+ and CD8+ T cell subsets. 4-1BB expression is induced upon PHA stimulation in both the naive (CD45RAhi-CD45ROlo/-) and the memory (CD45RAlo/-ROhi) T cell populations. Virtually all CD45RAhiROlo/- cells upon culture in PHA give rise to an intermediate CD45RAhiROhi 4-1BB+ transitional cell and subsequently CD45RAlo/-ROhi 4-1BBlo/- and CD45RAlo/-ROhi 4-1BBhi cells. In contrast, approximately 27% of CD45RAlo/-ROhi 4-1BB- cells when cultured in PHA for 24 hr acquire 4-1BB expression and all remain CD45RAlo/-ROhi.

Animals↗
PubMed1996

Polymerization of 5,6-dihydroxyindole-2-carboxylic acid to melanin by the pmel 17/silver locus protein.

Recent advances in melanogenesis have focused on the role of dihydroxyindole-2-carboxylic acid[(HO)2IndCOOH]. For example, it has been shown that formation of (HO)2IndCOOH from dopachrome is catalyzed by dopachrome tautomerase, that the melanogenic protein tyrosinase-related protein (TRP)-1 can oxidize (HO)2IndCOOH to its indole quinone, that (HO)2IndCOOH-melanins can be synthesized chemically, that mammalian melanins are naturally rich in (HO)2IndCOOH subunits, and that (HO)2IndCOOH is incorporated into melanins of melanomas in mice. The question thus emerges as to the mechanism(s) by which (HO)2IndCOOH and other precursors become incorporated into melanins in vivo. Accordingly, an activity was partially purified that catalyzed melanin formation with (HO)2IndCOOH as a substrate. Analyses of the (HO)2IndCOOH polymerization factor from Cloudman melanoma cells revealed the following: it was proteinaceous in that it was heat labile and destroyed by proteinase K; it was a glycoprotein in that it adhered to wheat germ agglutinin and was eluted with N-acetyl glucosamine; it was located predominantly in the melanosomal fraction of cell homogenates; the activity was reduced by exposure to the metal chelators EDTA and EGTA, but not by phenylthiourea, a tyrosinase inhibitor; the (HO)2IndCOOH polymerization reaction was inhibited by superoxide dismutase. In addition, the activity was found with the mouse pmel 17/silver locus protein immunopurified from human melanoma cells, and was significantly reduced in extracts of mouse melanocytes cultured from silver (si/si) mice compared to extracts from Si/Si melanocytes. In summary, an activity has been identified in human and mouse melanoma cells that catalyzes the superoxide-dependent polymerization of (HO)2IndCOOH to melanin in vitro, and appears to be a function of the pmel 17/silver protein of the human pmel 17 gene and the mouse silver locus.

Animals↗
PubMed1996

Characterization and subcellular localization of human Pmel 17/silver, a 110-kDa (pre)melanosomal membrane protein associated with 5,6,-dihydroxyindole-2-carboxylic acid (DHICA) converting activity.

Pmel 17 is preferentially expressed in pigment cells in a manner suggestive of involvement in melanin biosynthesis. The gene is identical to the silver (si) pigmentation locus in mice. We now produced a recombinant glutathione-S-transferase-human Pmel 17 infusion protein and raised polyclonal antibodies against it to confirm the ultrastructural location and presumed site of action predicted by the deduced primary structure of Pmel 17/silver, and to authenticate the specificity of the DHICA converting function as inherent to the silver-locus protein. Full-length Pmel 17 cDNA also produced in insect cells in a baculovirus expression vector to ensure that activity did not originate from a co-precipitated protein. Natural hPmel 17 from human melanoma cells has an approximate molecular size of 100 kDa. By immunoperoxidase electron microscopic cytochemistry, the antigen was localized to the limiting membranes of premelanosomes and presumed premelanogenic cytosolic vesicles and, to a minor extent, in the premelanosomal matrix. In an in vitro assay, both the natural and the recombinant Pmel 17 accelerated the conversion of DHICA to melanin. This activity was inhibited by the anti-Pmel 17 polyclonal antibodies, indicating that the acceleration of DHICA conversion by natural protein is genuine and cannot be due to contaminating complexed proteins. We suggest that in situ Pmel 17/silver is a component of a postulated premelanosomal/melanosomal complex of membrane-bound melanogenic oxidoreductive enzymes and cofactors, in analogy to the electron transfer chain in mitochondria.

Animals↗
PubMed1996

Genomic organization and FISH mapping of human Pmel 17, the putative silver locus.

The Pmel 17 gene is expressed preferentially in pigment cells. It has been mapped to human chromosome 12 pter-q21 and mouse chromosome 10, near the silver locus. The Pmel 17 gene contains an insertional mutation at its carboxyl terminus in the silver mouse, suggesting that the silver locus might correspond to the gene. In the current studies, we have isolated and characterized human Pmel 17 genomic clones and employed FISH mapping for a precise localization of this gene in the human chromosome. The FISH mapping placed the Pmel 17 gene at human chromosome 12 q12-q13. The human gene consists of nine exons and eight introns, and the entire coding region of the gene spans approximately 7.9 kb of the human chromosome 12. The putative functional domains, such as the signal sequence, histidine-rich, 26-amino acid repeats, cysteinerich, transmembrane and cytoplasmic domains, were encoded by separate exons. Cistranscription elements such as a TATA, a CAT and other potential elements for pigment cell-specific gene expression were found within 1100 base pairs of the 5' flanking region.

Amino Acid Sequence↗
PubMed1995

Potential role of 4-1BB in T cell activation. Comparison with the costimulatory molecule CD28.

The expression of the murine T cell Ag 4-1BB, a member of the TNF-R family, is induced by T cell activation. Previously, we and others had shown that signaling through 4-1BB enhanced proliferative T cell responses. To investigate a potential role for the interaction of 4-1BB with its ligand (4-1BBL) in T cell activation, we studied the ability of a soluble chimera of 4-1BB (4-1BBFc) to interfere with proliferative responses and cytokine production in models of activation dependent in intercellular interactions. The potential blocking effect of 4-1BBFc was compared with that of the chimeric molecule CTLA-4Ig, a reagent known to interfere with the interaction of CD28 (and/or CTLA-4) with B7 costimulatory receptors. In this study, we report that 4-1BBFc partially blocked both the activation of unfractionated splenocytes triggered by soluble anti-CD3 (anti-CD3s), and the more physiologically relevant responses to alloantigen. In addition, we show that both chimeric molecules partially blocked proliferative responses and IL-2 secretion by highly purified resting T cells activated with anti-CD3s in the presence of fixed accessory cells that express B7 receptors and 4-1BBL. Furthermore, in this model system, the blocking capacity of 4-1BBFc and CTLA-4Ig appears to correlate with the relative expression of their respective cognate receptors (4-1BBL and B7) on the accessory cell. Simultaneous addition of both blocking reagents produced an additive effect in the model systems studied.

Animals↗
PubMed1995

A novel chemokine, macrophage inflammatory protein-related protein-2, inhibits colony formation of bone marrow myeloid progenitors.

A new member of the beta-chemokine family, macrophage inflammatory protein (MIP)-related protein-2 (MRP-2) was isolated from a murine macrophage cell line, RAW 264.7. MRP-2 is composed of 122 amino acids of which the first 21 residues constitute a putative signal sequence. The putative mature protein is composed of 101 amino acids with a molecular weight of 11,600. MRP-2 is structurally similar to MIP-related protein-1 (MRP-1) (C10) and MIP-1 alpha. MRP-2 shows a 50.8% sequence identity at the protein level to MRP-1 and 46.3% identity to MIP-1 alpha. MRP-2 detects approximately 1.3 kilobase mRNA from monocyte and macrophage cell lines but does not detect the mRNA from T and B cells. The MRP-2 gene termed Scya9 was mapped to the central region of mouse chromosome 11 near the Scya1 and Scya2 genes, which are also members of the beta-chemokine superfamily. The Scya gene cluster was located between neurofibromatosis type 1 (Nf1) and myeloperoxidase (Mpo). rMRP-2 significantly suppressed colony formation by murine and human bone marrow granulocyte-macrophage (CFU-granulocyte-macrophage), erythroid (burst-forming unit-E), and multipotential (CFU-granulocyte-erythroid-macrophage-megakaryocyte) progenitor cells stimulated by combinations of growth factors.

Amino Acid Sequence↗
PubMed1995

Role of 4-1BB ligand in costimulation of T lymphocyte growth and its upregulation on M12 B lymphomas by cAMP.

K46J B lymphomas express a T cell costimulatory activity that is not inhibited by CTLA-4Ig, anti-B7-1, anti-B7-2, anti-intercellular adhesion molecule 1 or antibodies to heat stable antigen. In this paper we report that this costimulatory activity is mediated at least in part by 4-1BB ligand, a member of the tumor necrosis factor (TNF) gene family that binds to 4-1BB, a T cell activation antigen with homology to the TNF/nerve growth factor receptor family. A fusion protein between 4-1BB and alkaline phosphatase (4-1BB-AP) blocks T cell activation by K46J lymphomas in both an antigen-specific system and with polyclonally (anti-CD3) activated T cells. 4-1BB-AP also blocks antigen presentation by normal spleen cells. When the antigen-presenting cells express B7 molecules as well as 4-1BB ligand, we find that B7 molecules and 4-1BB-AP both contribute to T cell activation. These data suggest that 4-1BB ligand plays an important role in costimulation of IL-2 production and proliferation by T cells. The B lymphoma M12 expresses low levels of 4-1BB-L but can be induced to express higher levels by treatment of the B cells with cAMP, which also induces B7-1 and B7-2 in these cells. Thus cAMP appears to coordinately induce several costimulatory molecules on B cells.

4-1BB Ligand↗
PubMed1995

Mouse silver mutation is caused by a single base insertion in the putative cytoplasmic domain of Pmel 17.

This laboratory has established in previous studies that Pmel 17, a gene expressed specifically in melanocytes, maps near the silver coat color locus (si/si) on mouse chromosome 10. In the current study, we have focused on determining whether or not the si allele carries a mutation in Pmel 17. Pmel 17 cDNA clones, isolated from wild-type and si/si murine melanocyte cDNA libraries, were sequenced and compared. A single nucleotide (A) insertion was found in the putative cytoplasmic tail of the si/si Pmel 17 cDNA clone. This insertion is predicted to alter the last 24 amino acids at the C-terminus. Also predicted is the extension of the Pmel 17 protein by 12 residues because a new termination signal created downstream from the wild-type reading frame. The mutation was confirmed by the sequence of the PCR-amplified genomic region flanking and including the mutation site. The fact that si/si Pmel 17 was not recognized by antibodies directed toward the C-terminal 15 amino acids of wild-type Pmel 17, indicated a defect in this region. We conclude from these results that silver pmel 17 protein has a major defect at the carboxyl terminus. The chromosomal location and the identification of a potentially pathologic mutation in si-Pmel 17 support our conclusion that Pmel 17 is encoded at the silver locus.

Amino Acid Sequence↗
PubMed1995

Regulation of 4-1BB expression by cell-cell interactions and the cytokines, interleukin-2 and interleukin-4.

4-1BB expression increased gradually following T cell activation, and by day 3 post-stimulation with immobilized anti-CD3 (anti-CD3i) or concanavalin A (Con A), splenic T cells were routinely 35-45% 4-1BB+ by flow cytometric analysis. 4-1BB was expressed on activated CD8+, CD4+, CD28+ and CD45RB+ T cells. Optimal 4-1BB expression was seen by day 6 post-stimulation and was cell density dependent. When T cells were cultured for 6 days at 1 x 10(6)/well in a 24-well plate with anti-CD3i, 82% of the cells were 4-1BB+. In contrast, at lower cell densities (4 x 10(5), 2 x 10(5) and 1 x 10(5)), optimal 4-1BB expression was observed only if the cultures were supplemented with recombinant interleukin-2 (IL-2) or recombinant IL-4 (IL-4). In agreement, with these results, modes of inducing endogenous IL-2 production such as cross-linking the costimulatory molecule, CD28, or the addition of syngeneic accessory cells to T cells activated with anti-CD3i, resulted in high levels of 4-1BB expression. The addition of interleukin-1 alpha (IL-1 alpha) or interferon-gamma (IFN-gamma) did not increase 4-1BB expression on anti-CD3i-activated T cells. In addition, if T cells were incubated with IL-2, IL-4, IL-1 alpha, IFN-gamma or anti-CD28 alone, no 4-1BB expression was induced. T cells activated with soluble anti-CD3 (anti-CD3s) in the presence of IL-2, IL-4, or accessory cells, did not express higher levels of 4-1BB on their cell surface. These data suggest that initial events crucial for efficient T cell activation, such as signals delivered through the T cell receptor/CD3 complex and the CD28 molecule, are instrumental in regulating subsequent 4-1BB expression.

Animals↗
PubMed1995

Characterization of human homologue of 4-1BB and its ligand.

The human homologue of 4-1BB (H4-1BB) cDNA was isolated from PMA plus ionomycin-treated human peripheral T-cell cDNA libraries. The amino acid sequence deduced from the nucleotide sequence showed that the protein is composed of 255 amino acids with 2 potential N-linked glycosylation sites. The molecular weight of its protein backbone is calculated to be 27 kDa. The H4-1BB contains features such as signal sequence and transmembrane domain, indicating that it is a receptor protein. This protein showed 60% identity of amino acid sequence to mouse 4-1BB. In the cytoplasmic domain there are 5 regions of amino acid sequences conserved from mouse to human, indicating that these residues might be important in the 4-1BB function. H4-1BB mRNA was detected in unstimulated peripheral blood T cells and was inducible in T-cell lines such as Jurkat and CEM. H4-1BB-AP, a fusion protein between the H4-1BB extracellular domain and alkaline phosphatase, was used to identify the ligand for the H4-1BB. Although the H4-1BB ligand was detected in both T and B cells of human peripheral blood, the ligand was preferentially expressed in primary B cells and B-cell lines. Daudi, a B-cell lymphoma, was one of the B-cell lines that carried a higher number of ligands. Scatchard analysis showed that the Kd = 1.4 x 10(9) M and the number of ligands in Daudi cell was 4.2 x 10(3).

3T3 Cells↗
PubMed1995

Myeloid progenitor cell regulatory effects of vascular endothelial cell growth factor.

Vascular endothelial cell growth factor (VEGF) is a ligand for the tyrosine kinase receptor Flk-1/KDR and Flt1 and is considered to be an endothelial cell specific mitogen that plays an important role in angiogenesis. Since Flk-1 mRNA has been detected in primitive and more mature hematopoietic cells, recombinant human VEGF was evaluated for its influence on hematopoiesis, which was assayed as in vitro colony formation by myeloid progenitor cells from human bone marrow. VEGF enhanced colony formation by mature subsets of granulocyte-macrophage and erythroid progenitor cells that had been stimulated with a colony stimulating factor. In contrast, VEGF inhibited colony formation by more immature subsets of granulocyte-macrophage, erythroid and multipotential progenitor cells synergistically stimulated to proliferate with a colony stimulating factor and either steel factor or the ligand for the Flt-3 receptor tyrosine kinase. VEGF produced effects similar to those given above on purified CD34 progenitor cells from bone marrow and VEGF effects were neutralized by VEGF antibodies. However, when assessed for effects on single sorted CD34 cells, VEGF only enhanced or suppressed colony formation by granulocyte-macrophage progenitor cells and the amplitude of the response was less than that observed when populations of these cells were tested. In the single cell assays, VEGF had no effect on colony formation by erythroid or multipotential progenitors. These results suggest that the effects of VEGF, which were not species specific, are mediated by both direct and indirect actions on the progenitors and thereby identify new activities for this important factor.

Animals↗
PubMed1995

Turtle lung cells produce a melanization-stimulating activity that promotes melanocytic differentiation of avian neural crest cells.

We found previously that neural crest cells in turtle embryos migrated into the lung buds and melanocytes were located in the lungs. The finding suggested to us that the lungs provide a stimulatory factor(s) to the differentiation of neural crest cells into melanocytes. We have established lung cell lines to facilitate analysis of the interactions of neural crest cells with the environment in melanocyte development. One cell line, TLC-2, was found to produce a putative melanization-stimulating activity (MSA), which promoted the melanocyte differentiation in vitro of avian neural crest cells. The TLC-2-derived MSA was different from that of basic fibroblast growth factor (bFGF), alpha-melanocyte stimulating hormone (alpha-MSH), and steel factor (SLF). Its molecular weight was estimated to be within the range of 150 kD. Our findings suggest that MSA may be a novel factor exercising a positive control over melanocyte differentiation.

Animals↗
PubMed1994

The Pmel 17/silver locus protein. Characterization and investigation of its melanogenic function.

The silver mutation in mice causes progressive graying of hair due to the loss of functional follicular melanocytes. Recently the silver locus gene (called Pmel 17) has been cloned; its encoded product shares homology with a chick melanosomal matrix protein and a bovine retinal pigment epithelial protein. Although the sequence of the silver gene and the correlation of its expression with pigment production have been reported, its function in melanogenesis is still unknown. In an effort to characterize that function, we have synthesized the predicted carboxyl-terminal peptide of the mouse Pmel 17 protein and generated a rabbit polyclonal antibody (alpha PEP13) to it; that antibody recognized the silver protein specifically. The immunoaffinity-purified silver protein lacked all of the known melanogenic catalytic activities which other tyrosinase-related proteins (TRP) have, nor did it appear to modulate any of those TRP activities. Metabolic labeling experiments demonstrated that the silver protein disappears in vivo within a few hours, indicating that it is rapidly degraded, or quickly processed to lose its carboxyl terminus. Cross-reactivity experiments showed that a recently reported anti-melanosomal matrix protein antibody (alpha MX) also recognizes the silver protein, although at a different epitope from that of alpha PEP13. Using Western immunoblotting, we analyzed subcellular fractions isolated from B16 F10 melanoma cells and found that the silver protein was rich in the melanosome fraction but was absent from coated vesicles which deliver TRPs to melanosomes. These results suggest that the silver locus product is a melanosomal matrix protein which may contribute to melanogenesis as a structural protein, although the possibility remains that it also has a novel catalytic function in melanogenesis.

Amino Acid Sequence↗
PubMed1994

Genomic organization and chromosomal localization of the T-cell antigen 4-1BB.

4-1BB is an inducible T cell surface receptor which belongs to the nerve growth factor receptor superfamily, a group of cysteine-rich cell-surface proteins. 4-1BB is a 30-kDa glycoprotein and exists as both a monomer and a 55-kDa dimer on the T cell surface. Cross-linking 4-1BB with monoclonal antibody resulted in the 2- to 10-fold enhancement of T cell proliferation. We have isolated and characterized 4-1BB genomic clones and have found that the 4-1BB gene contains two different 5' untranslated regions, which are used alternately to form the 4-1BB mRNA. The two 5' UTRs were encoded in the same chromosome and were separated from one another by an intron of approximately 2.5 kb. The entire gene spans approximately 13 kb of mouse chromosome 4. 4-1BB gene consists of 10 exons and 9 introns, in which there are two exons for 5' untranslated regions and 8 exons for coding region. Most of the putative functional domains were encoded by separate exons. 4-1BB extracellular domain contains four potential C6 (CXn C XX C XX CXn C Xn C) motifs, of which the first motif is partial and the third is distinct from those of nerve growth factor receptor or TNF receptor 1. A comparison of exon-intron organization among the genes of the nerve growth factor receptor family indicated that most C6 motif is interrupted by an intron.

Amino Acid Sequence↗
PubMed1994

4-1BB T-cell antigen binds to mature B cells and macrophages, and costimulates anti-mu-primed splenic B cells.

4-1BB is expressed on activated murine T cells and may function as an accessory signaling molecule during T-cell activation. To identify putative 4-1BB ligands, a fusion protein consisting of the extracellular domain of 4-1BB fused to human placental alkaline phosphatase (4-1BB-AP) was constructed. Alkaline phosphatase activity could then be used as an indicator of the relative amount of bound 4-1BB. These studies indicated that 4-1BB-AP specifically bound to the surface of various mature B and macrophage cell lines. 4-1BB-AP bound at low levels to T cell lines (non-activated and anti-CD3-activated), pre-B-cell lines, and an immature macrophage cell line. 4-1BB-AP did not bind to a glial tumor cell line, HeLa cells, or COS cells. In addition, 4-1BB-AP bound at higher levels to F(ab')2 anti-mu-activated primary B cells compared to anti-CD3-activated primary T cells. Scatchard analysis indicated that the A20 B cell lymphoma expressed 3680 binding sites per cell with a Kd of 1.86 nM. Affinity cross-linking studies demonstrated that a major cell surface species of 120 kDa bound to 4-1BB-AP; 4-1BB-AP also bound to a minor species of approximately 60 kDa. The addition of paraformaldehyde-fixed SF21 cells expressing recombinant 4-1BB synergized with F(ab')2 anti-mu in inducing splenic B cell proliferation suggesting that 4-1BB may function as a regulator of B cell growth.

Animals↗