| 1. |
- Gjertsson, Inger, 1962, et al.
(författare)
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The role of B cell CD22 expression in Staphylococcus aureus arthritis and sepsis
- 2004
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Ingår i: Microbes Infect. - 1286-4579. ; 6:4, s. 377-82
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Tidskriftsartikel (refereegranskat)abstract
- Severe Staphylococcus aureus infections give rise to a pronounced antigen-specific and polyclonal B cell response with elevated serum immunoglobulin levels. However, it has been difficult to correlate the antibody levels with the clinical outcome of sepsis and/or arthritis concerning both protection and pathogenic aspects. Earlier studies have shown that macrophages and neutrophils are of great importance for bacterial clearance. However, deletion of the complete B cell compartment affected neither S. aureus-induced arthritis nor survival. MZ B cells are believed to be of importance for clearance of blood-borne antigens and have been implicated in protection against S. aureus infections. CD22 is a B-cell-specific inhibitory receptor binding to alpha2,6-linked sialic acids, and deficiency in CD22 leads to a 75% reduction of the MZ B cell compartment. CD22-/- mice and congeneic controls were inoculated intravenously with an arthritogenic dose of live S. aureus. No differences between the groups were detected regarding frequency and severity of arthritis, survival, bacterial clearance, or induction of inflammatory response. This study shows explicitly that a reduced MZ B cell compartment in the absence of CD22 expression does not interfere with the inflammatory response during S. aureus infection.
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| 2. |
- Nitschke, L, et al.
(författare)
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Deletion of the DQ52 element within the Ig heavy chain locus leads to a selective reduction in VDJ recombination and altered D gene usage
- 2001
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Ingår i: Journal of immunology (Baltimore, Md. : 1950). - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 166:4, s. 2540-2552
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Tidskriftsartikel (refereegranskat)abstract
- The process of V(D)J recombination that leads to the assembly of Ig gene segments is tightly controlled during B cell differentiation. Two germline transcripts, one of which (μ0) originates from the promoter region of DQ52, may control the accessibility of the heavy chain locus. Here, we present the analysis of a mouse line in which the DQ52 gene together with its regulatory sequences is deleted by a Cre/loxP-based strategy. In F1 (DQ52+/−) mice, the use of the JH3 and JH4 elements in DJ or VDJ junctions of the DQ52− allele was strongly reduced in both the bone marrow pre-B and spleen cells, while the JH1 and JH2 elements were used with normal frequencies. In addition, IgM+ B cells of bone marrow and spleen used the DQ52− allele less frequently. On DJ joints of the DQ52− allele, there was 2 times less processing of JH3 ends, which resulted in clearly increased addition of P nucleotides. Although the use of D elements in DJ joints was quite similar, an altered D repertoire was found in VDJ joints of the DQ52− allele. In splenic B cells of the DQ52−/− mouse the amino acid distribution of the CDR3 was skewed, probably to compensate for the altered processing of JH3 ends. Thus, we have shown an interesting selective effect of the DQ52 region on controlling accessibility to 3′ JH elements on the Ig locus, which also seems to influence the processing of DJ joints. We propose a model in which the DQ52 promoter region enhances the induction of secondary DJ rearrangements.
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