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B-1a B cells that link the innate and adaptive immune responses are lacking in the absence of the spleen.

Wardemann H, Boehm T, Dear N, Carsetti R - J. Exp. Med. (2002)

Bottom Line: Transfer experiments demonstrate that lack of these cells, as opposed to the absence of the spleen per se, is associated with an inability to mount a rapid immune response against streptococcal polysaccharides.Thus, absence of the spleen and the associated increased susceptibility to streptococcal infections is correlated with lack of B-1a B cells.These findings reveal a hitherto unknown role of the spleen in generating and maintaining the B-1a B cell pool.

View Article: PubMed Central - PubMed

Affiliation: Department of Developmental Immunology, Max-Planck Institute for Immunobiology, Freiburg 79108, Germany.

ABSTRACT
Splenectomized individuals are prone to overwhelming infections with encapsulated bacteria and splenectomy of mice increases susceptibility to streptococcal infections, yet the exact mechanism by which the spleen protects against such infections is unknown. Using congenitally asplenic mice as a model, we show that the spleen is essential for the generation of B-1a cells, a B cell population that cooperates with the innate immune system to control early bacterial and viral growth. Splenectomy of wild-type mice further demonstrated that the spleen is also important for the survival of B-1a cells. Transfer experiments demonstrate that lack of these cells, as opposed to the absence of the spleen per se, is associated with an inability to mount a rapid immune response against streptococcal polysaccharides. Thus, absence of the spleen and the associated increased susceptibility to streptococcal infections is correlated with lack of B-1a B cells. These findings reveal a hitherto unknown role of the spleen in generating and maintaining the B-1a B cell pool.

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The spleen is important for the generation of peritoneal B-1a cells in the mouse. (A) The total number of peritoneal cells is shown for 16-wk-old C57BL/6 (n = 10) and Hox11- (n = 10) mice. Hox11+/− and C57BL/6 mice do not differ in any of the peritoneal B cell compartments; thus C57BL/6 were used as controls throughout the paper. (B) Peritoneal cavity cells of one C57BL/6 and one Hox11- mouse were stained with antibodies against IgM, IgD, CD5, and B220 and analyzed by flow-cytometry. The relative expression of IgM and IgD can be used to discriminate IgMposIgDdull B-1 (gate 1) from IgMdullIgDpos B-2 cells (gate 2, left panels). Based on the expression of IgM and IgD, B-1 and B-2 cells were gated as indicated and analyzed for the expression of B220 and CD5 to further distinguish between CD5posB220dull B-1a cells (top region, bottom right panels) and the CD5negB220pos B-1b population (bottom region, bottom right panels). While B-1b cells are normal in Hox11- mice, the B220dullCD5pos B-1a population is absent. B-2 cells (gate 2) are CD5negB220pos mature B cells (top right panels). The CD5posB220pos B-1a population that remains in Hox11- mice is indicated with an arrow. (C) The proportion of B-1a cells in the peritoneum of C57BL/6 (n = 8) and Hox11- (n = 8) are shown. Peritoneal B cells (IgMpos and/or IgDpos) were measured by flow cytometric analysis and IgMposIgDdullCD5posB220dull were classified as B-1a cells. (D) Relative serum IgM levels in blood of C57BL/6 (n = 10) and Hox11- mice (n = 9) were determined by anti-IgM ELISA. Each data point represents the relative serum IgM level of one mouse measured at a 1:1,000 dilution.
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fig1: The spleen is important for the generation of peritoneal B-1a cells in the mouse. (A) The total number of peritoneal cells is shown for 16-wk-old C57BL/6 (n = 10) and Hox11- (n = 10) mice. Hox11+/− and C57BL/6 mice do not differ in any of the peritoneal B cell compartments; thus C57BL/6 were used as controls throughout the paper. (B) Peritoneal cavity cells of one C57BL/6 and one Hox11- mouse were stained with antibodies against IgM, IgD, CD5, and B220 and analyzed by flow-cytometry. The relative expression of IgM and IgD can be used to discriminate IgMposIgDdull B-1 (gate 1) from IgMdullIgDpos B-2 cells (gate 2, left panels). Based on the expression of IgM and IgD, B-1 and B-2 cells were gated as indicated and analyzed for the expression of B220 and CD5 to further distinguish between CD5posB220dull B-1a cells (top region, bottom right panels) and the CD5negB220pos B-1b population (bottom region, bottom right panels). While B-1b cells are normal in Hox11- mice, the B220dullCD5pos B-1a population is absent. B-2 cells (gate 2) are CD5negB220pos mature B cells (top right panels). The CD5posB220pos B-1a population that remains in Hox11- mice is indicated with an arrow. (C) The proportion of B-1a cells in the peritoneum of C57BL/6 (n = 8) and Hox11- (n = 8) are shown. Peritoneal B cells (IgMpos and/or IgDpos) were measured by flow cytometric analysis and IgMposIgDdullCD5posB220dull were classified as B-1a cells. (D) Relative serum IgM levels in blood of C57BL/6 (n = 10) and Hox11- mice (n = 9) were determined by anti-IgM ELISA. Each data point represents the relative serum IgM level of one mouse measured at a 1:1,000 dilution.

Mentions: We have previously shown that the spleen plays a major role in the late phases of B cell development. Transitional 1 (T1) B cells, recently emigrated from the bone marrow, accumulate in the spleen and here differentiate to transitional 2 (T2) and mature B cells (19). To further study the function of the spleen in the development of B cells, we analyzed congenitally asplenic Hox11- mice (12, 13). Of the major B cell and T cell populations from bone marrow, lymph node, and thymus analyzed by FACS®, we could not detect any gross phenotypic abnormalities. A minor increase in the number of T1 B cells in bone marrow and peripheral blood was observed, perhaps reflecting a shortage of space, as these cells normally collect in the spleen. Reductions were also observed in the proportion of mature B cells in blood, lymph node, and bone marrow (data not shown). This confirms the role of the spleen in the generation of normal numbers of mature B cells. The most striking finding, however, was a large reduction in the total cell number in the peritoneal cavity of Hox11- mice (8.9 ± 2.0 × 106 in C57BL/6, 5.1 ± 1.0 × 106 in Hox11-, Fig. 1 A). However, in the peritoneal lymphocyte population there was no significant difference in the proportion of total B cells between C57BL/6 and Hox11- (59.5% ± 5.7% in C57BL/6, 69.1% ± 6.6% in Hox11-). Thus, nonB cells including T cells but also myeloid cells are reduced in the peritoneal cavity of Hox11- mice.


B-1a B cells that link the innate and adaptive immune responses are lacking in the absence of the spleen.

Wardemann H, Boehm T, Dear N, Carsetti R - J. Exp. Med. (2002)

The spleen is important for the generation of peritoneal B-1a cells in the mouse. (A) The total number of peritoneal cells is shown for 16-wk-old C57BL/6 (n = 10) and Hox11- (n = 10) mice. Hox11+/− and C57BL/6 mice do not differ in any of the peritoneal B cell compartments; thus C57BL/6 were used as controls throughout the paper. (B) Peritoneal cavity cells of one C57BL/6 and one Hox11- mouse were stained with antibodies against IgM, IgD, CD5, and B220 and analyzed by flow-cytometry. The relative expression of IgM and IgD can be used to discriminate IgMposIgDdull B-1 (gate 1) from IgMdullIgDpos B-2 cells (gate 2, left panels). Based on the expression of IgM and IgD, B-1 and B-2 cells were gated as indicated and analyzed for the expression of B220 and CD5 to further distinguish between CD5posB220dull B-1a cells (top region, bottom right panels) and the CD5negB220pos B-1b population (bottom region, bottom right panels). While B-1b cells are normal in Hox11- mice, the B220dullCD5pos B-1a population is absent. B-2 cells (gate 2) are CD5negB220pos mature B cells (top right panels). The CD5posB220pos B-1a population that remains in Hox11- mice is indicated with an arrow. (C) The proportion of B-1a cells in the peritoneum of C57BL/6 (n = 8) and Hox11- (n = 8) are shown. Peritoneal B cells (IgMpos and/or IgDpos) were measured by flow cytometric analysis and IgMposIgDdullCD5posB220dull were classified as B-1a cells. (D) Relative serum IgM levels in blood of C57BL/6 (n = 10) and Hox11- mice (n = 9) were determined by anti-IgM ELISA. Each data point represents the relative serum IgM level of one mouse measured at a 1:1,000 dilution.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
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fig1: The spleen is important for the generation of peritoneal B-1a cells in the mouse. (A) The total number of peritoneal cells is shown for 16-wk-old C57BL/6 (n = 10) and Hox11- (n = 10) mice. Hox11+/− and C57BL/6 mice do not differ in any of the peritoneal B cell compartments; thus C57BL/6 were used as controls throughout the paper. (B) Peritoneal cavity cells of one C57BL/6 and one Hox11- mouse were stained with antibodies against IgM, IgD, CD5, and B220 and analyzed by flow-cytometry. The relative expression of IgM and IgD can be used to discriminate IgMposIgDdull B-1 (gate 1) from IgMdullIgDpos B-2 cells (gate 2, left panels). Based on the expression of IgM and IgD, B-1 and B-2 cells were gated as indicated and analyzed for the expression of B220 and CD5 to further distinguish between CD5posB220dull B-1a cells (top region, bottom right panels) and the CD5negB220pos B-1b population (bottom region, bottom right panels). While B-1b cells are normal in Hox11- mice, the B220dullCD5pos B-1a population is absent. B-2 cells (gate 2) are CD5negB220pos mature B cells (top right panels). The CD5posB220pos B-1a population that remains in Hox11- mice is indicated with an arrow. (C) The proportion of B-1a cells in the peritoneum of C57BL/6 (n = 8) and Hox11- (n = 8) are shown. Peritoneal B cells (IgMpos and/or IgDpos) were measured by flow cytometric analysis and IgMposIgDdullCD5posB220dull were classified as B-1a cells. (D) Relative serum IgM levels in blood of C57BL/6 (n = 10) and Hox11- mice (n = 9) were determined by anti-IgM ELISA. Each data point represents the relative serum IgM level of one mouse measured at a 1:1,000 dilution.
Mentions: We have previously shown that the spleen plays a major role in the late phases of B cell development. Transitional 1 (T1) B cells, recently emigrated from the bone marrow, accumulate in the spleen and here differentiate to transitional 2 (T2) and mature B cells (19). To further study the function of the spleen in the development of B cells, we analyzed congenitally asplenic Hox11- mice (12, 13). Of the major B cell and T cell populations from bone marrow, lymph node, and thymus analyzed by FACS®, we could not detect any gross phenotypic abnormalities. A minor increase in the number of T1 B cells in bone marrow and peripheral blood was observed, perhaps reflecting a shortage of space, as these cells normally collect in the spleen. Reductions were also observed in the proportion of mature B cells in blood, lymph node, and bone marrow (data not shown). This confirms the role of the spleen in the generation of normal numbers of mature B cells. The most striking finding, however, was a large reduction in the total cell number in the peritoneal cavity of Hox11- mice (8.9 ± 2.0 × 106 in C57BL/6, 5.1 ± 1.0 × 106 in Hox11-, Fig. 1 A). However, in the peritoneal lymphocyte population there was no significant difference in the proportion of total B cells between C57BL/6 and Hox11- (59.5% ± 5.7% in C57BL/6, 69.1% ± 6.6% in Hox11-). Thus, nonB cells including T cells but also myeloid cells are reduced in the peritoneal cavity of Hox11- mice.

Bottom Line: Transfer experiments demonstrate that lack of these cells, as opposed to the absence of the spleen per se, is associated with an inability to mount a rapid immune response against streptococcal polysaccharides.Thus, absence of the spleen and the associated increased susceptibility to streptococcal infections is correlated with lack of B-1a B cells.These findings reveal a hitherto unknown role of the spleen in generating and maintaining the B-1a B cell pool.

View Article: PubMed Central - PubMed

Affiliation: Department of Developmental Immunology, Max-Planck Institute for Immunobiology, Freiburg 79108, Germany.

ABSTRACT
Splenectomized individuals are prone to overwhelming infections with encapsulated bacteria and splenectomy of mice increases susceptibility to streptococcal infections, yet the exact mechanism by which the spleen protects against such infections is unknown. Using congenitally asplenic mice as a model, we show that the spleen is essential for the generation of B-1a cells, a B cell population that cooperates with the innate immune system to control early bacterial and viral growth. Splenectomy of wild-type mice further demonstrated that the spleen is also important for the survival of B-1a cells. Transfer experiments demonstrate that lack of these cells, as opposed to the absence of the spleen per se, is associated with an inability to mount a rapid immune response against streptococcal polysaccharides. Thus, absence of the spleen and the associated increased susceptibility to streptococcal infections is correlated with lack of B-1a B cells. These findings reveal a hitherto unknown role of the spleen in generating and maintaining the B-1a B cell pool.

Show MeSH
Related in: MedlinePlus