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B cell activation i...
B cell activation in vitro: thymus-dependent immune responses and bacterial cell surface proteins
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- Axcrona, Karol (författare)
- Lund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups
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(creator_code:org_t)
- ISBN 9162829408
- 1998
- Engelska 144 s.
- Relaterad länk:
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https://lup.lub.lu.s...
Abstract
Ämnesord
Stäng
- In this thesis aspects of peripheral B lymphocyte differentiation were studied. Through in vitro experiments, B lymphocyte activation was assessed. B lymphocytes express immunoglobulin (Ig) specific for a certain antigen on the cell surface, and when surface Ig is crosslinked by an antigen, the cell is activated. Antigens giving rise to a T cell dependent immune response are internalized by the B cell, degraded, and presented on MHC II. In order to differentiate, an activated B cell has to interact with a T cell bearing a T cell receptor specific for the same antigen. During B cell/T cell interaction a crosstalk mediated by cell surface molecules is initiated. For example, the CD40/CD40 ligand (CD40L) receptor interaction plays a critical role in B cell activation; genetically engineered animals deficient for either the CD40L or CD40, lack germinal centres, Ig switch and immunological memory. When B cells were activated with anti-CD40 monoclonal antibodies (mAbs) together with anti-CD21 mAbs coupled to Sepharose differentiation to Ig secretion was detected. Addition of anti-CD40 mAbs to lipopolysaccharide (LPS) stimulated B cells was, however, shown to inhibit B cell differentiation in the same manner as addition of anti-Ig mAbs to LPS treated cultures. Further, B cells prestimulated with anti-CD40 were shown to undergo apoptosis when restimulated with anti-Ig. Because of the pivotal role of the CD40L/CD40 interaction in T cell dependent immune responses, the CD40L promoter was analyzed. The CD40L promoter and deletants of that promoter were cloned into an expression vector containing the structural gene for luciferase, as a reporter gene. Upon transient transfection into Jurkat T cells CD40L promoter function was shown to be dependent on signaling via the T cell receptor and CD28. A 270 bp region upstream of the translational start was shown to suffice for full promoter activity. A putative CD28 responsive DNA element distinct from the one in the IL-2 promoter was identified. Streptococcal Ig-binding surface proteins L, M1, and H were shown to bind various cells of the hematopoetic lineage; proteins L and H coupled to Sepharose induced B cell proliferation, whereas protein H coupled to Sepharose also induced B cell differentiation. Soluble protein H was shown to be taken up by T and B cells and transported to the nucleus. Protein H was found to interact with nucleophosmin/B23 (NPM), a protein previously shown to traffic from the cytoplasm to the nucleus, but which was isolated from a membrane preparation from Jurkat T cells. In the nucleus protein H was found to interact with hnRNP A2/B1 and the SET protein. Affinities of protein H with NPM and a nuclear extract prepared from Jurkat T cells were determined. Lastly, when murine B cells were stimulated with LPS, addition of protein H was shown to exert a cytostatic effect.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Nyckelord
- nuclear transport
- bacterial Ig-binding proteins
- CD40L promoter
- CD21
- Ig
- B lymphocyte activation in vitro
- CD40
- Immunology
- serology
- transplantation
- Immunologi
- serologi
Publikations- och innehållstyp
- dok (ämneskategori)
- vet (ämneskategori)
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