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CD22, an inhibitory co-receptor of the B-cell receptor, shows a B-cell-specific expression pattern and is expressed on most B-cell lymphomas. The anti-CD22 antibody Epratuzumab is in clinical trials for B-cell non-Hodgkin lymphoma and systemic lupus erythematosus, but shows a mostly unknown mode of action. We generated a new mouse model that expresses human CD22 instead of murine CD22 (Huki CD22 mice), in which human CD22 can be targeted. Expression of human CD22 on the B cells of Huki CD22 mice does not generally interfere with B-cell development. However, Huki CD22 mice show a reduction of the population of mature recirculating B cells in the bone marrow and reduced transitional and marginal zone B cells in the spleen, phenotypes resembling that of CD22-deficient mice. Similarly, enhanced BCR-induced Ca 2+ signalling is observed in Huki CD22 mice, which also mount normal immune responses toward different classes of antigens. Huki CD22 B cells show a normal anti-hCD22 antibody-mediated endocytosis. In conclusion, human CD22 cannot fully substitute for murine CD22 functions, possibly due to the changed intracellular tail of the protein or due to lower expression levels. Huki CD22 mice are a valuable new model for both antibody-and immunotoxin-mediated targeting of human CD22.Keywords: B-cell lymphoma r B-cell signalling r Siglecs r SLE Supporting Information available online IntroductionCo-stimulating proteins or co-receptors can modulate the B-cell receptor (BCR) signal. One of them is CD22, a member of the Siglec family (sialic acid binding immunoglobulin-like lectins). Siglecs bind to sialic acids, which are usually expressed on cell surfaces and in the extracellular milieu [1,2]. All Siglecs recognise sialic acids, but they vary in their affinity for different glycosidelinkages. CD22 prefers sialic acids in α2,6-linkage [3][4][5]. It is an Correspondence: Prof. Lars Nitschke e-mail: nitschke@biologie.uni-erlangen.de inhibitory co-receptor for BCR-induced calcium (Ca 2+ ) signalling. CD22 carries inhibitory ITIM-signalling motifs, which recruit the tyrosine phosphatase SHP-1 that is responsible for the inhibitory function of CD22. CD22 can bind to α 2,6-linked sialic acidcontaining ligands in cis and in trans. This ligand binding can modulate the signalling function of CD22 [3][4][5].The murine CD22 and the human CD22 protein share about 60% sequence homology. The human CD22 gene is located on chromosome 19 in the human genome, the mouse gene is located on chromosome 7. The human and the murine CD22 are expressed from the pre-B-cell stage to the mature B-cell stage. CD22 is downregulated on plasma cells [5]. It is also expressed on a majority of all B-cell lymphomas [6], for example, CD22 is expressed on 65% of the B-cell acute lymphoblastic leukaemia [7]. Differentwww.eji-journal.eu 3010 Miriam Wöhner et al. Eur. J. Immunol. 2012. 42: 3009-3018 immunotoxins use anti-CD22-antibodies to target these lymphoma and leukaemia cells. As a toxin component, these antibodies are linked to bacterial or plant toxin...

Latissimus dorsi tendon transfer is an established method in the treatment of the nonrepairable rotator cuff tear. Originally, the muscle has to realize retroversion and internal rotation of the arm. After tendon transfer the function of the muscle is completely different from this -the muscle supports the elevation of the arm now. To take over the new function, patients need regulary for 9 to 12 months. In some studies this fact was controlled by surface electromyography (SEMG).In our study we examined two groups of patients with a constant SEMG score 12 weeks after tendon transfer. One group received (a = 30) common rehabilitation and the other patients (a = 23) worked with SEMG-feedback therapy.

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