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Identification of CD22 ligands on bone marrow sinusoidal endothelium implicated in CD22-dependent homing of recirculating B cells.

Nitschke L, Floyd H, Ferguson DJ, Crocker PR - J. Exp. Med. (1999)

Bottom Line: Previous studies showed that CD22-deficient mice had a strongly reduced population of mature recirculating B cells in the bone marrow despite normal B cell development.Treatment of mice with either CD22-Fc or affinity-purified anti-CD22 antibody led to an approximately 50% reduction in mature recirculating B cells in the bone marrow without affecting numbers in the spleen.Finally, consistent with the notion that CD22 is a homing receptor, we show that compared with wild-type mice, CD22-deficient animals have a lower number of immunoglobulin M-secreting plasma cells in the bone marrow.

View Article: PubMed Central - PubMed

Affiliation: Institute for Virology and Immunobiology, University of Würzburg, 97078 Würzburg, Germany.

ABSTRACT
CD22 is a B cell-specific transmembrane protein known to function as a negative regulator of B cell signaling. It has also been implicated in cell adhesion through recognition of alpha2,6-linked sialic acids on glycans of target cells. Previous studies showed that CD22-deficient mice had a strongly reduced population of mature recirculating B cells in the bone marrow despite normal B cell development. Using a soluble recombinant form of the receptor (CD22-Fc), we demonstrate here that sialylated ligands for CD22 are expressed on sinusoidal endothelial cells of murine bone marrow but not on endothelial cells in other tissues examined. Injection of CD22-Fc revealed that the CD22 ligands in the bone marrow were accessible to the circulation. Treatment of mice with either CD22-Fc or affinity-purified anti-CD22 antibody led to an approximately 50% reduction in mature recirculating B cells in the bone marrow without affecting numbers in the spleen. Finally, consistent with the notion that CD22 is a homing receptor, we show that compared with wild-type mice, CD22-deficient animals have a lower number of immunoglobulin M-secreting plasma cells in the bone marrow.

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CD22-deficient mice  have a reduced number of plasma  cells in the bone marrow and an  enhanced number in the spleen.  The number of IgM- and IgG- secreting plasma cells in bone  marrow (BM) and spleen (Spl) of  wild-type (black bars) and CD22-deficient mice (hatched bars) was  determined by an Elispot assay.  All differences shown are significant with P < 0.01, except for  bone marrow IgG at P < 0.05  (Student's t test, n = 3). The mean level of IgM was two times higher in  the serum of CD22-deficient mice, whereas there was no difference in IgG  levels between CD22-deficient and wild-type mice. One typical experiment out of three performed is shown.
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Figure 3: CD22-deficient mice have a reduced number of plasma cells in the bone marrow and an enhanced number in the spleen. The number of IgM- and IgG- secreting plasma cells in bone marrow (BM) and spleen (Spl) of wild-type (black bars) and CD22-deficient mice (hatched bars) was determined by an Elispot assay. All differences shown are significant with P < 0.01, except for bone marrow IgG at P < 0.05 (Student's t test, n = 3). The mean level of IgM was two times higher in the serum of CD22-deficient mice, whereas there was no difference in IgG levels between CD22-deficient and wild-type mice. One typical experiment out of three performed is shown.

Mentions: The bone marrow is known to be a major site of Ig secretion by plasma cells (22). To address the question of whether the lack of recirculating B cells in the bone marrow of CD22-deficient mice would also affect plasma cells, we determined their number in the bone marrow and spleen of CD22-deficient and control mice. In the bone marrow of CD22-deficient mice, there was a significant reduction of IgM-secreting plasma cells, whereas these cells were increased in the spleen compared with wild-type mice (Fig. 3). In this experiment, the number of IgG- secreting plasma cells was also reduced in the bone marrow. In two other experiments, the reduction of IgG-secreting plasma cells in the bone marrow of CD22-deficient mice was less pronounced, whereas IgM plasma cells were consistently reduced (not shown).


Identification of CD22 ligands on bone marrow sinusoidal endothelium implicated in CD22-dependent homing of recirculating B cells.

Nitschke L, Floyd H, Ferguson DJ, Crocker PR - J. Exp. Med. (1999)

CD22-deficient mice  have a reduced number of plasma  cells in the bone marrow and an  enhanced number in the spleen.  The number of IgM- and IgG- secreting plasma cells in bone  marrow (BM) and spleen (Spl) of  wild-type (black bars) and CD22-deficient mice (hatched bars) was  determined by an Elispot assay.  All differences shown are significant with P < 0.01, except for  bone marrow IgG at P < 0.05  (Student's t test, n = 3). The mean level of IgM was two times higher in  the serum of CD22-deficient mice, whereas there was no difference in IgG  levels between CD22-deficient and wild-type mice. One typical experiment out of three performed is shown.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2193059&req=5

Figure 3: CD22-deficient mice have a reduced number of plasma cells in the bone marrow and an enhanced number in the spleen. The number of IgM- and IgG- secreting plasma cells in bone marrow (BM) and spleen (Spl) of wild-type (black bars) and CD22-deficient mice (hatched bars) was determined by an Elispot assay. All differences shown are significant with P < 0.01, except for bone marrow IgG at P < 0.05 (Student's t test, n = 3). The mean level of IgM was two times higher in the serum of CD22-deficient mice, whereas there was no difference in IgG levels between CD22-deficient and wild-type mice. One typical experiment out of three performed is shown.
Mentions: The bone marrow is known to be a major site of Ig secretion by plasma cells (22). To address the question of whether the lack of recirculating B cells in the bone marrow of CD22-deficient mice would also affect plasma cells, we determined their number in the bone marrow and spleen of CD22-deficient and control mice. In the bone marrow of CD22-deficient mice, there was a significant reduction of IgM-secreting plasma cells, whereas these cells were increased in the spleen compared with wild-type mice (Fig. 3). In this experiment, the number of IgG- secreting plasma cells was also reduced in the bone marrow. In two other experiments, the reduction of IgG-secreting plasma cells in the bone marrow of CD22-deficient mice was less pronounced, whereas IgM plasma cells were consistently reduced (not shown).

Bottom Line: Previous studies showed that CD22-deficient mice had a strongly reduced population of mature recirculating B cells in the bone marrow despite normal B cell development.Treatment of mice with either CD22-Fc or affinity-purified anti-CD22 antibody led to an approximately 50% reduction in mature recirculating B cells in the bone marrow without affecting numbers in the spleen.Finally, consistent with the notion that CD22 is a homing receptor, we show that compared with wild-type mice, CD22-deficient animals have a lower number of immunoglobulin M-secreting plasma cells in the bone marrow.

View Article: PubMed Central - PubMed

Affiliation: Institute for Virology and Immunobiology, University of Würzburg, 97078 Würzburg, Germany.

ABSTRACT
CD22 is a B cell-specific transmembrane protein known to function as a negative regulator of B cell signaling. It has also been implicated in cell adhesion through recognition of alpha2,6-linked sialic acids on glycans of target cells. Previous studies showed that CD22-deficient mice had a strongly reduced population of mature recirculating B cells in the bone marrow despite normal B cell development. Using a soluble recombinant form of the receptor (CD22-Fc), we demonstrate here that sialylated ligands for CD22 are expressed on sinusoidal endothelial cells of murine bone marrow but not on endothelial cells in other tissues examined. Injection of CD22-Fc revealed that the CD22 ligands in the bone marrow were accessible to the circulation. Treatment of mice with either CD22-Fc or affinity-purified anti-CD22 antibody led to an approximately 50% reduction in mature recirculating B cells in the bone marrow without affecting numbers in the spleen. Finally, consistent with the notion that CD22 is a homing receptor, we show that compared with wild-type mice, CD22-deficient animals have a lower number of immunoglobulin M-secreting plasma cells in the bone marrow.

Show MeSH
Related in: MedlinePlus