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Meningeal Infiltration of the Spinal Cord by Non-Classically Activated B Cells is Associated with Chronic Disease Course in a Spontaneous B Cell-Dependent Model of CNS Autoimmune Disease.

Dang AK, Tesfagiorgis Y, Jain RW, Craig HC, Kerfoot SM - Front Immunol (2015)

Bottom Line: These clusters were typically found adjacent to white matter lesions and their presence was associated with a chronic disease course.Extensive investigation of these clusters by histology did not identify features of lymphoid follicles, including organization of T and B cells into separate zones, CD35(+) follicular dendritic cells, or germinal centers.Nevertheless, they were CD62L(lo) and CD80(hi) compared to lymph node B cells suggesting that they were at least partly activated and primed to present antigen.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University Canada , London, ON , Canada.

ABSTRACT
We characterized B cell infiltration of the spinal cord in a B cell-dependent spontaneous model of central nervous system (CNS) autoimmunity that develops in a proportion of mice with mutant T and B cell receptors specific for myelin oligodendrocyte glycoprotein. We found that, while males are more likely to develop disease, females are more likely to have a chronic rather than monophasic disease course. B cell infiltration of the spinal cord was investigated by histology and FACs. CD4(+) T cell infiltration was pervasive throughout the white and in some cases gray matter. B cells were almost exclusively restricted to the meninges, often in clusters reminiscent of those described in human multiple sclerosis. These clusters were typically found adjacent to white matter lesions and their presence was associated with a chronic disease course. Extensive investigation of these clusters by histology did not identify features of lymphoid follicles, including organization of T and B cells into separate zones, CD35(+) follicular dendritic cells, or germinal centers. The majority of cluster B cells were IgD(+) with little evidence of class switch. Consistent with this, B cells isolated from the spinal cord were of the naïve/memory CD38(hi) CD95(lo) phenotype. Nevertheless, they were CD62L(lo) and CD80(hi) compared to lymph node B cells suggesting that they were at least partly activated and primed to present antigen. Therefore, if meningeal B cells contribute to CNS pathology in autoimmunity, follicular differentiation is not necessary for the pathogenic mechanism.

No MeSH data available.


Related in: MedlinePlus

Characterization of B cells in the lymph nodes and spinal cords of 2D2 IgHMOG mice with sEAE. (A) Lymph nodes and spinal cords were harvested from healthy wild type mice as well as 2D2 IgHMOG mice that had either developed disease (sick – 20–30 days post onset) or not (healthy – age matched). Cells were prepared and analyzed by FACS. CD45R+ cells were first selected. An example of the gating strategy to identify Plasma cells [(A) – left] and B cells with a GC phenotype [(A) – right] from the CD45R+ pool is shown for lymph node and spinal cord cells isolated from a single sick mouse. (B) Quantification of CD95hi CD38lo germinal center B cells in the lymph nodes of wild type and healthy or sick 2D2 IgHMOG mice. Each symbol represents an individual mouse. *p < 0.05. (C) Comparison of CD62L (left) and CD80 (right) expression by CD45R+ CD19+ CD138− B cells isolated from lymph nodes or the CNS of the same mouse. Each symbol represents an individual sick mouse. ***p < 0.001 as determined by paired Student’s t-test. One representative of two experiments shown.
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Figure 3: Characterization of B cells in the lymph nodes and spinal cords of 2D2 IgHMOG mice with sEAE. (A) Lymph nodes and spinal cords were harvested from healthy wild type mice as well as 2D2 IgHMOG mice that had either developed disease (sick – 20–30 days post onset) or not (healthy – age matched). Cells were prepared and analyzed by FACS. CD45R+ cells were first selected. An example of the gating strategy to identify Plasma cells [(A) – left] and B cells with a GC phenotype [(A) – right] from the CD45R+ pool is shown for lymph node and spinal cord cells isolated from a single sick mouse. (B) Quantification of CD95hi CD38lo germinal center B cells in the lymph nodes of wild type and healthy or sick 2D2 IgHMOG mice. Each symbol represents an individual mouse. *p < 0.05. (C) Comparison of CD62L (left) and CD80 (right) expression by CD45R+ CD19+ CD138− B cells isolated from lymph nodes or the CNS of the same mouse. Each symbol represents an individual sick mouse. ***p < 0.001 as determined by paired Student’s t-test. One representative of two experiments shown.

Mentions: Previous studies employing the 2D2 IgHMOG model focused primarily on T cell activation (29, 30, 33) and information about B cell activation in this or other spontaneous models is very limited. Immune responses that incorporate both T and B cell recognition of antigen typically result in a GC response. Consistent with this, significantly more CD95hi CD38lo GC B cells were present in lymph nodes harvested from sick 2D2 IgHMOG mice (~3 weeks post onset) compared to wild type or age-matched 2D2 IgHMOG that did not develop sEAE (Figures 3A,B). It should be noted that, with disease progression and severity, we observed lymph node atrophy and in some cases little remaining GC response could be detected (not shown).


Meningeal Infiltration of the Spinal Cord by Non-Classically Activated B Cells is Associated with Chronic Disease Course in a Spontaneous B Cell-Dependent Model of CNS Autoimmune Disease.

Dang AK, Tesfagiorgis Y, Jain RW, Craig HC, Kerfoot SM - Front Immunol (2015)

Characterization of B cells in the lymph nodes and spinal cords of 2D2 IgHMOG mice with sEAE. (A) Lymph nodes and spinal cords were harvested from healthy wild type mice as well as 2D2 IgHMOG mice that had either developed disease (sick – 20–30 days post onset) or not (healthy – age matched). Cells were prepared and analyzed by FACS. CD45R+ cells were first selected. An example of the gating strategy to identify Plasma cells [(A) – left] and B cells with a GC phenotype [(A) – right] from the CD45R+ pool is shown for lymph node and spinal cord cells isolated from a single sick mouse. (B) Quantification of CD95hi CD38lo germinal center B cells in the lymph nodes of wild type and healthy or sick 2D2 IgHMOG mice. Each symbol represents an individual mouse. *p < 0.05. (C) Comparison of CD62L (left) and CD80 (right) expression by CD45R+ CD19+ CD138− B cells isolated from lymph nodes or the CNS of the same mouse. Each symbol represents an individual sick mouse. ***p < 0.001 as determined by paired Student’s t-test. One representative of two experiments shown.
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Related In: Results  -  Collection

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Figure 3: Characterization of B cells in the lymph nodes and spinal cords of 2D2 IgHMOG mice with sEAE. (A) Lymph nodes and spinal cords were harvested from healthy wild type mice as well as 2D2 IgHMOG mice that had either developed disease (sick – 20–30 days post onset) or not (healthy – age matched). Cells were prepared and analyzed by FACS. CD45R+ cells were first selected. An example of the gating strategy to identify Plasma cells [(A) – left] and B cells with a GC phenotype [(A) – right] from the CD45R+ pool is shown for lymph node and spinal cord cells isolated from a single sick mouse. (B) Quantification of CD95hi CD38lo germinal center B cells in the lymph nodes of wild type and healthy or sick 2D2 IgHMOG mice. Each symbol represents an individual mouse. *p < 0.05. (C) Comparison of CD62L (left) and CD80 (right) expression by CD45R+ CD19+ CD138− B cells isolated from lymph nodes or the CNS of the same mouse. Each symbol represents an individual sick mouse. ***p < 0.001 as determined by paired Student’s t-test. One representative of two experiments shown.
Mentions: Previous studies employing the 2D2 IgHMOG model focused primarily on T cell activation (29, 30, 33) and information about B cell activation in this or other spontaneous models is very limited. Immune responses that incorporate both T and B cell recognition of antigen typically result in a GC response. Consistent with this, significantly more CD95hi CD38lo GC B cells were present in lymph nodes harvested from sick 2D2 IgHMOG mice (~3 weeks post onset) compared to wild type or age-matched 2D2 IgHMOG that did not develop sEAE (Figures 3A,B). It should be noted that, with disease progression and severity, we observed lymph node atrophy and in some cases little remaining GC response could be detected (not shown).

Bottom Line: These clusters were typically found adjacent to white matter lesions and their presence was associated with a chronic disease course.Extensive investigation of these clusters by histology did not identify features of lymphoid follicles, including organization of T and B cells into separate zones, CD35(+) follicular dendritic cells, or germinal centers.Nevertheless, they were CD62L(lo) and CD80(hi) compared to lymph node B cells suggesting that they were at least partly activated and primed to present antigen.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University Canada , London, ON , Canada.

ABSTRACT
We characterized B cell infiltration of the spinal cord in a B cell-dependent spontaneous model of central nervous system (CNS) autoimmunity that develops in a proportion of mice with mutant T and B cell receptors specific for myelin oligodendrocyte glycoprotein. We found that, while males are more likely to develop disease, females are more likely to have a chronic rather than monophasic disease course. B cell infiltration of the spinal cord was investigated by histology and FACs. CD4(+) T cell infiltration was pervasive throughout the white and in some cases gray matter. B cells were almost exclusively restricted to the meninges, often in clusters reminiscent of those described in human multiple sclerosis. These clusters were typically found adjacent to white matter lesions and their presence was associated with a chronic disease course. Extensive investigation of these clusters by histology did not identify features of lymphoid follicles, including organization of T and B cells into separate zones, CD35(+) follicular dendritic cells, or germinal centers. The majority of cluster B cells were IgD(+) with little evidence of class switch. Consistent with this, B cells isolated from the spinal cord were of the naïve/memory CD38(hi) CD95(lo) phenotype. Nevertheless, they were CD62L(lo) and CD80(hi) compared to lymph node B cells suggesting that they were at least partly activated and primed to present antigen. Therefore, if meningeal B cells contribute to CNS pathology in autoimmunity, follicular differentiation is not necessary for the pathogenic mechanism.

No MeSH data available.


Related in: MedlinePlus