Lars Nitschke

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Inhibitory co-receptors downmodulate B-cell receptor (BCR) signalling by setting a signalling threshold that prevents overstimulation of B cells. Activation of these inhibitory co-receptors occurs by phosphorylation on their cytoplasmic inhibitory immunoreceptor tyrosine-based inhibition motifs (ITIMs), followed by recruitment of the tyrosine phosphatase(More)
We describe a mouse strain in which B cell development relies either on the expression of membrane-bound immunoglobulin (Ig) gamma1 or mu heavy chains. Progenitor cells expressing gamma1 chains from the beginning generate a peripheral B cell compartment of normal size with all subsets, but a partial block is seen at the pro- to pre-B cell transition.(More)
BACKGROUND . Antibody responses are triggered by binding of antigen to the B-cell antigen receptor (BCR). The strength of the resulting signal determines the outcome of the response, which may vary from the induction of tolerance to the antigen, to the production of specific high-affinity antibodies. Additional cell-surface proteins assist the BCR in its(More)
B cells use immunoglobulin M (IgM) and IgD as antigen receptors, but after contact with antigen they can switch and use IgG, IgA, or IgE. In mice lacking the transmembrane and cytoplasmic domains of IgE, serum IgE is reduced by more than 95 percent and, after immunization, specific responses are negligible. In mice lacking most of the cytoplasmic tail of(More)
Murine (m) Siglec-E and mSiglec-F are recently discovered murine sialic acid-binding Ig-like lectins with tyrosine-based inhibitory signaling motifs. They are postulated to be the orthologs of human (h) siglec-7, -8 or -9 and siglec-5, respectively. We report here the first detailed characterization of mSiglec-E, and compare its expression pattern with(More)
The inhibitory coreceptors CD22 and CD72 downmodulate B-cell receptor (BCR) signaling and function as a molecular switch, determining whether antigen-stimulated B cells undergo apoptosis or proliferation. These coreceptors carry an intrinsic property for associating with the BCR, and this association is crucial for the initiation of signal inhibition(More)
Spontaneous loss-of-function mutations in the protein-tyrosine phosphatase Shp1 cause the motheaten phenotype, characterized by widespread inflammation and autoimmunity. Because Shp1 is expressed in all hematopoietic cells, it has been unclear which aspects of the motheaten phenotypes are primary effects of Shp1 deficiency. We generated mice(More)
The interaction of CD22 with glycoprotein ligands bearing the Siaalpha2,6Gal-R sequence is believed to modulate its function as a regulator of B cell signaling. Although a commercial sialoside-polyacrylamide (PAA) probe, NeuAc- alpha2,6Gal-PAA, has facilitated studies on ligand binding by human CD22, murine CD22 binds instead with high affinity to(More)
B cell antigen receptor (BCR) engagement can lead to many different physiologic outcomes. To achieve an appropriate response, the BCR signal is interpreted in the context of other stimuli and several additional receptors on the B cell surface participate in the modulation of the signal. Two members of the Siglec (sialic acid-binding immunoglobulin-like(More)
CD22 is a B-cell-restricted transmembrane protein, which acts as a negative regulator of B-cell signalling. CD22 also has lectin-like adhesive properties. When expressed on transfected fibroblasts, it is capable of mediating adhesion to other cells via recognition of cell-surface glycoconjugates terminating in alpha2,6-linked sialic acids. In previous(More)