| 1. |
|
|
| 2. |
|
|
| 3. |
- Bemark, Mats, 1967, et al.
(författare)
-
Limited clonal relatedness between gut IgA plasma cells and memory B cells after oral immunization
- 2016
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding how memory B cells are induced and relate to long-lived plasma cells is important for vaccine development. Immunity to oral vaccines has been considered short-lived because of a poor ability to develop IgA B-cell memory. Here we demonstrate that long-lived mucosal IgA memory is readily achieved by oral but not systemic immunization in mouse models with NP hapten conjugated with cholera toxin and transfer of B1-8high /GFP+ NP-specific B cells. Unexpectedly, memory B cells are poorly related to long-lived plasma cells and less affinity-matured. They are α4β7-integrin+ CD73+ PD-L2+ CD80+ and at systemic sites mostly IgM+, while 80% are IgA+ in Peyer's patches. On reactivation, most memory B cells in Peyer's patches are GL7+, but expand in germinal centres and acquire higher affinity and more mutations, demonstrating strong clonal selection. CCR9 expression is found only in Peyer's patches and appears critical for gut homing. Thus, gut mucosal memory possesses unique features not seen after systemic immunization. © 2016 The Author(s).
|
|
| 4. |
- Bergqvist, Peter, 1978, et al.
(författare)
-
Re-utilization of germinal centers in multiple Peyer's patches results in highly synchronized, oligoclonal, and affinity-matured gut IgA responses.
- 2013
-
Ingår i: Mucosal immunology. - : Elsevier BV. - 1935-3456 .- 1933-0219. ; 6, s. 122-135
-
Tidskriftsartikel (refereegranskat)abstract
- Whereas gut IgA responses to the microbiota may be multi-centered and diverse, little is known about IgA responses to T-cell-dependent antigens following oral immunizations. Using a novel approach, gut IgA responses to oral hapten (4-hydroxy-3-nitrophenyl)acetyl-cholera toxin (NP-CT) conjugates were followed at the cellular and molecular level. Surprisingly, these responses were highly synchronized, strongly oligoclonal, and dominated by affinity matured cells. Extensive lineage trees revealed clonal relationships between NP-specific IgA cells in gut inductive and effector sites, suggesting expansion of the same B-cell clone in multiple Peyer's patches (PPs). Adoptive transfer experiments showed that this was achieved through re-utilization of already existing germinal centers (GCs) in multiple PPs by previously activated GC GL7(+) B cells, provided oral NP-CT was given before cell transfer. Taken together, these results explain why repeated oral immunizations are mandatory for an effective oral vaccine.Mucosal Immunology advance online publication 11 July 2012. doi:10.1038/mi.2012.56.
|
|
| 5. |
- Johansson, S, et al.
(författare)
-
Natural killer cell education in mice with single or multiple major histocompatibility complex class I molecules
- 2005
-
Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 201:7, s. 1145-1155
-
Tidskriftsartikel (refereegranskat)abstract
- The ability of murine NK cells to reject cells lacking self MHC class I expression results from an in vivo education process. To study the impact of individual MHC class I alleles on this process, we generated mice expressing single MHC class I alleles (Kb, Db, Dd, or Ld) or combinations of two or more alleles. All single MHC class I mice rejected MHC class I–deficient cells in an NK cell–dependent way. Expression of Kb or Dd conveyed strong rejection of MHC class I–deficient cells, whereas the expression of Db or Ld resulted in weaker responses. The educating impact of weak ligands (Db and Ld) was further attenuated by the introduction of additional MHC class I alleles, whereas strong ligands (Kb and Dd) maintained their educating impact under such conditions. An analysis of activating and inhibitory receptors in single MHC class I mice suggested that the educating impact of a given MHC class I molecule was controlled both by the number of NK cells affected and by the strength of each MHC class I–Ly49 receptor interaction, indicating that NK cell education may be regulated by a combination of qualitative and quantitative events.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Lycke, Nils Y, 1954, et al.
(författare)
-
Re-utilization of germinal centers in multiple PP results in highly synchronized, oligoclonal and affinity matured gut IgA responses
- 2012
-
Ingår i: Journal of Immunology. - 0022-1767. ; 188
-
Tidskriftsartikel (refereegranskat)abstract
- Whereas recent studies have pointed to multi-centered and diverse gut IgA responses to the microbiota, little information is available on IgA responses following oral immunization with T cell-dependent antigens. Here we have addressed how gut IgA responses develop using a novel approach where NP-hapten was conjugated to cholera toxin (CT), which allowed us to follow, at the molecular level, the site of initiation, expansion, differentiation and distribution of a specific IgA B cell response. Clonal relationships and affinity maturation of specific IgA cells at gut inductive and effector sites were investigated. Unexpectedly, we found gut IgA B cell responses to be oligoclonal and dominated by high affinity maturation. Extensive lineage trees of gut NP-specific IgA cells were generated, revealing strong clonal relationships throughout the entire gut mucosal immune system. Thus, clonally related IgA cells were found in Peyer’s patches, mesenteric lymph nodes and the small and large intestine, suggesting an effective expansion and selection process. This was achieved through synchronization of multiple PP hosting the same high affinity B cell clones. Adoptive transfer experiments showed that this was possible through re-utilization of already existing germinal centers (GC) in multiple PP by previously activated GC GL7+ B cells. The re-utilization required that oral antigen was given prior to cell transfer.
|
|
| 9. |
|
|
| 10. |
|
|
