Ontogeny of reticular framework of white pulp and marginal zone in human spleen: immunohistochemical studies of fetal spleens from the 17th to 40th week of gestation

2009 ◽  
Vol 336 (2) ◽  
pp. 287-297 ◽  
Author(s):  
Takashi Satoh ◽  
Eiichi Sakurai ◽  
Hiroshi Tada ◽  
Tomoyuki Masuda
1998 ◽  
Vol 188 (9) ◽  
pp. 1691-1703 ◽  
Author(s):  
Stuart G. Tangye ◽  
Yong-Jun Liu ◽  
Gregorio Aversa ◽  
Joseph H. Phillips ◽  
Jan E. de Vries

Memory B cells isolated from human tonsils are characterized by an activated cell surface phenotype, localization to mucosal epithelium, expression of somatically mutated immunoglobulin (Ig) variable (V) region genes, and a preferential differentiation into plasma cells in vitro. In spleens of both humans and rodents, a subset of memory B cells is believed to reside in the marginal zone of the white pulp. Similar to tonsil-derived memory B cells, splenic marginal zone B cells can be distinguished from naive follicular B cells by a distinct cell surface phenotype and by the presence of somatic mutations in their Ig V region genes. Although differences exist between human naive and memory B cells, no cell surface molecules have been identified that positively identify all memory B cells. In this study, we have examined the expression of the receptor-type protein tyrosine phosphatase CD148 on human B cells. CD148+ B cells present in human spleen exhibited characteristics typical of memory B cells. These included an activated phenotype, localization to the marginal zone, the expression of somatically mutated Ig V region genes, and the preferential differentiation into plasma cells. In contrast, CD148− B cells appeared to be naive B cells due to localization to the mantle zone, the expression of surface antigens typical of unstimulated B cells, and the expression of unmutated Ig V region genes. Interestingly, CD148+ B cells also coexpressed CD27, whereas CD148− B cells were CD27−. These results identify CD148 and CD27 as markers which positively identify memory B cells present in human spleen. Thus, assessing expression of these molecules may be a convenient way to monitor the development of memory B cell responses in immunocompromised individuals or in vaccine trials.


2003 ◽  
Vol 51 (5) ◽  
pp. 655-663 ◽  
Author(s):  
Birte Steiniger ◽  
Lars Rüttinger ◽  
Peter J. Barth

The precise arrangement of B- and T-lymphocytes in the different compartments of the human splenic white pulp is still largely unknown. We therefore performed a 3D reconstruction of 150 serial sections of a representative adult human spleen alternately stained for CD3 and CD20. The results indicate that the T-cell regions of human spleens may be interrupted by B-cell follicles. Therefore, there is no continuous periarteriolar lymphatic T-cell sheath (PALS) around white pulp arterioles. An arteriole may be surrounded by T-lymphocytes at one level, then run across a follicle without any T-cells around, and finally re-enter a T-cell region. T- and B-cell compartments are intricately interdigitated in the human splenic white pulp. CD4+ T-lymphocytes and the typical fibroblasts of the T-cell region may extend as a thin shell at the follicular surface within the marginal zone. On the other hand, IgD++ B-cells continue from the follicular outer marginal zone along the surface of the T-cell region. Our findings indicate that the microanatomy of the splenic white pulp differs between humans and rodents. This may have consequences for the immigration of recirculating lymphocytes and for initial interactions among antigen-specific T- and B-lymphocytes.


Blood ◽  
2001 ◽  
Vol 97 (11) ◽  
pp. 3470-3477 ◽  
Author(s):  
Dorian McIlroy ◽  
Christelle Troadec ◽  
Fernanda Grassi ◽  
Assia Samri ◽  
Benoı̂t Barrou ◽  
...  

Although the mouse spleen dendritic cell (DC) is perhaps the most intensively studied DC type, little has been published concerning its human equivalent. In this report, rare event flow cytometry and in situ immunofluorescence were used to study the surface phenotype and distribution of HLA-DR+CD3−14−16−19− human spleen DC. Spleens from organ donors with different clinical histories were used. Most (81% ± 9%; n = 14) spleen DCs expressed high levels of the integrin CD11c. CD11c+ DCs were distributed in 3 distinct regions—the peri-arteriolar T-cell zones, the B-cell zones, and the marginal zone, where they formed a ring of cells surrounding the white pulp, just inside a ring of CD14+ red pulp macrophages, apparently more regularly organized than the previously described marginating DC population in the mouse spleen. The T-cell zones contained CD86+ DCs, among which a subpopulation expressed CD83. These mature/activated CD86+DCs represented a minority (12% ± 8%) of total spleen DCs in most organ donors: most spleen DCs are immature. In 3 of 18 (17%) donors, however, most (54%-81%) of spleen DCs were CD86+, suggesting that in vivo DC activation had occurred. In one donor, a radical shift in DC distribution from the marginal zone to the T-cell zones was also observed. This activation of spleen DCs in vivo was reminiscent of the effects of experimental microbial product injection in mice, and it seemed to correlate with bacterial infection or multiple trauma.


1995 ◽  
Vol 182 (2) ◽  
pp. 559-566 ◽  
Author(s):  
D K Dunn-Walters ◽  
P G Isaacson ◽  
J Spencer

The splenic marginal zone (MGZ), which surrounds the mantle zone (MTZ) in human splenic white pulp, contains a phenotypically and morphologically distinct population of B cells. The origin of MGZ B cells is uncertain. Whereas some experiments in rodents have suggested that they are a distinct cell lineage responsible for the immune response to T-independent type 2 antigens, others have suggested that they are memory B cells derived from a germinal center (GC) response. The progeny of a GC reaction is expected to have rearranged immunoglobulin (Ig) genes that are mutated. The distribution of mutations would be expected to reflect the selection of Ig by its affinity for antigen. We have analyzed rearranged Ig heavy chain variable region (VH) 6 and VH 4.21 genes in MGZ and MTZ B cells microdissected from frozen sections of human spleen to determine whether these genes have the properties of an affinity-selected memory B cell population. MTZ B cells contained germline Ig VH genes, confirming previous reports and providing an internal control for mutational analysis. MGZ B cells contained Ig VH genes that were mutated, showing that these cells had been subjected to a mutational mechanism characteristically active in the GC. The rearranged VH 6 genes showed patterns of mutation indicative of an antigen selection process, whereas the distribution of mutations in VH 4.21 genes was not characteristic of gene selection by conventional T-dependent antigen. Our studies provide the first evidence that the human splenic MGZ is a reservoir of memory B cells.


1996 ◽  
Vol 33 (3) ◽  
pp. 282-289 ◽  
Author(s):  
M. V. Palmer ◽  
N. F. Cheville ◽  
F. M. Tatum

BALB/C mice were inoculated intraperitoneally with suspensions of Brucella abortus strains 2308 or RB51 or an htrA mutant. Spleens were examined on postinoculation day (PID) 2, 4, 7, 10, 15, 21, 30, and 60. Brucellae were cultured in high numbers from the spleens of mice infected with strains 2308 or htrA through PID 60; however, mice infected with strain RB51 cleared the infection between PID 30 and PID 60. Histopathologic changes in spleens from 2308-infected mice were characterized by marked accumulations of macrophages, which expanded marginal zones beginning as early as PID 7 and persisting through PID 60. Morphometric analysis showed a decrease in splenic white pulp in 2308-infected mice at PID 10, which correlated with the peak of bacterial infection. Although this decrease was significant ( P < 0.05) when compared with values at the previous (PID 7) and the following (PID 15) time periods, it was not significantly different from white pulp values noted at PID 2 or PID 4 or the values for control spleens. Spleens from RB51-infected mice showed only mild to moderate accumulations of macrophages in marginal zone areas during the peak of RB51 infection (PID 7-10). Morphometric analysis of RB51-infected spleens showed a decrease in white pulp area, which coincided with peak bacterial numbers. However, this decrease was not significant ( P > 0.05). Spleens from mice infected with the htrA mutant showed moderate to marked accumulations of macrophages in marginal zone areas, which persisted through PID 60. Multifocal necrosis in lymphoid follicles as early as PID 4 was seen in both htrA and 2308 infection. Morphometric analysis of htrA-infected spleens revealed no significant decrease in white pulp and no obvious correlation with bacterial numbers in the spleen. These results suggest that virulent B. abortus does not induce lymphoid depletion significantly below those values seen in noninfected mice; thus, the possible role of lymphoid depletion in the pathogenesis of brucellosis remains questionable.


Rare Tumors ◽  
2009 ◽  
Vol 1 (2) ◽  
pp. 169-170
Author(s):  
Noriko Koga ◽  
Masanori Noguchi ◽  
Fukuko Moriya ◽  
Kouichi Ohshima ◽  
Nobuyuki Yoshitake ◽  
...  

We report a case of primary mucosa-associated lymphoid tissue (MALT) lymphoma of the prostate. A 67-year-old man presented with urinary obstruction and an elevated prostate-specific antigen (PSA) level. A physical examination revealed mild prostate enlargement and no lymphadenopathy. A needle biopsy and immunohistochemical studies of the prostate were performed, which revealed marginal zone B-cell MALT-type lymphoma. A bone marrow aspiration and biopsy did not show involvement by lymphoma. Magnetic resonance imaging (MRI) of the abdomen and the pelvis revealed no lymphadenopathy or ascites. There was no involvement of other sites by lymphoma. The patient was diagnosed and staged as extranodal marginal zone B-cell MALT-type lymphoma of the prostate, low grade and stage I. The patient received external beam radiation therapy to the prostate with a total dose of 3600cGy in 22 fractions, and became free of disease within the following 15 months.


1996 ◽  
Vol 184 (5) ◽  
pp. 1927-1937 ◽  
Author(s):  
L Martínez-Pomares ◽  
M Kosco-Vilbois ◽  
E Darley ◽  
P Tree ◽  
S Herren ◽  
...  

Ligands for the cysteine-rich (CR) domain of the mannose receptor (MR) were detected by incubating murine tissues with a chimeric protein containing CR fused to the Fc region of human IgG1 (CR-Fc). In naive mice, CR-Fc bound to sialoadhesin+, F4/80low/-, macrosialin+ macrophages (M phi) in spleen marginal zone (metallophilic M phi) and lymph node subcapsular sinus. Labeling was also observed in B cell areas of splenic white pulp. Western blotting analysis of spleen and lymph nodes lysates revealed a restricted number of molecules that interacted specifically with CR-Fc. In immunized mice, labeling was upregulated on germinal centers in splenic white pulp and follicular areas of lymph nodes. Kinetic analysis of the pattern of CR-Fc labeling in lymph nodes during a secondary immune response to ovalbumin showed that CR ligand expression migrated towards B cell areas, associated with cells displaying distinctive dendritic morphology, and accumulated in developing germinal centers. These studies suggest that MR+ cells or MR-carbohydrate-containing antigen complexes could be directed towards areas where humoral immune responses take place, through the interaction of the MR CR domain with molecules expressed in specialized macrophage populations and antigen transporting cells.


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