Core 2 branching β1,6-N-acetylglucosaminyltransferase and high endothelial cell N-acetylglucosamine-6-sulfotransferase exert differential control over B- and T-lymphocyte homing to peripheral lymph nodes

Blood ◽  
2004 ◽  
Vol 104 (13) ◽  
pp. 4104-4112 ◽  
Author(s):  
Jean-Marc Gauguet ◽  
Steven D. Rosen ◽  
Jamey D. Marth ◽  
Ulrich H. von Andrian
Keyword(s):  
T Cells ◽  
Endothelial Cell ◽  
T Cell ◽  
B Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Lymphocyte Homing ◽  
High Endothelial Venules ◽  
Rolling Velocity ◽  
Peripheral Lymph

Abstract Blood-borne lymphocyte trafficking to peripheral lymph nodes (PLNs) depends on the successful initiation of rolling interactions mediated by L-selectin binding to sialomucin ligands in high endothelial venules (HEVs). Biochemical analysis of purified L-selectin ligands has identified posttranslational modifications mediated by Core2GlcNAcT-I and high endothelial cell GlcNAc-6-sulfotransferase (HECGlcNAc6ST). Consequently, lymphocyte migration to PLNs of C2GlcNAcT-I-/- and HEC-GlcNAc6ST-/- mice was reduced; however, B-cell homing was more severely compromised than T-cell migration. Accordingly, intravital microscopy (IVM) of PLN HEVs revealed a defect in B-cell tethering and increased rolling velocity (Vroll) in C2GlcNAcT-I-/- mice that was more pronounced than it was for T cells. By contrast, B- and T-cell tethering was normal in HEC-GlcNAc6ST-/- HEVs, but Vroll was accelerated, especially for B cells. The increased sensitivity of B cells to glycan deficiencies was caused by lower expression levels of L-selectin; L-selectin+/- T cells expressing L-selectin levels equivalent to those of B cells exhibited intravascular behavior similar to that of B cells. These results demonstrate distinct functions for C2GlcNAcT-I and HEC-GlcNAc6ST in the differential elaboration of HEV glycoproteins that set a threshold for the amount of L-selectin needed for lymphocyte homing. (Blood. 2004;104:4104-4112)

scholarly journals A Rare Case of T-Cell Histiocyte Rich Large B-Cell Lymphoma of the Thyroid in a Patient With Hashimotos

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A879-A880
Author(s):  
Abir Zainal ◽  
Jhansi Maradana ◽  
Mira Torres
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Thyroid Gland ◽  
Lymph Nodes ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Introduction: T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare form of large B-cell lymphoma, which usually involves the lymph nodes exclusively. We describe a patient with Hashimoto’s thyroiditis who was discovered to have THRLBCL arising from the thyroid. Clinical Case: A 78-year-old female with a history of Hashimoto’s thyroiditis noted increase in the size of her left thyroid lobe for two months despite normal TSH on Levothyroxine, prompting an ultrasound which revealed several enlarged left sided cervical lymph nodes and an enlarged left thyroid gland. Cytology from an FNA of a left level 3 lymph node showed atypical lymphoid infiltrate featuring scattered large atypical cells in a background of small lymphocytes. Immunohistochemical testing was PAX5+, CD30- and CD15-. Cytology from an FNA of left thyroid revealed identical changes and immunohistochemistry demonstrated PAX5+ and CD20+. Concurrent flow cytometric studies demonstrated increased CD4 to CD8 ratio among T cells. Excisional biopsy of a left cervical lymph node confirmed a diagnosis of THRLBCL. PET/CT exhibited lymphadenopathy above her diaphragm and splenic involvement. Her bone marrow biopsy was negative for involvement. She was deemed Stage III with international prognostic index (IPI) of 2 corresponding with low-intermediate risk. She was commenced on chemotherapy R-CHOP with plan to complete 6 cycles. Discussion: THRLBCL is characterized by scattered atypical B lymphocytes on a background of T lymphocytes and histiocytes. Usually, T-cells are predominantly CD8+, in contrast to our patient. Some studies identified cases of predominant CD4+ and PD1+ T cells. Cytology revealed scattered small B-cells and large B-cells, a feature that is not typically seen in THRLBCL. A diagnosis of diffuse transformation of nodular lymphocyte predominant Hodgkin lymphoma was considered but the diffuse proliferation outside of CD21+ and involvement of the thyroid is not compatible with such diagnosis. Similarly, a diagnosis of follicular helper T-cell lymphoma with admixed large B-cells was considered but while PD1+ CD4+ T cells are present, there was no aberrant antigen expression by flow cytometry or T cell clonality. THRLBCL mainly involves lymph nodes and presents at advanced Ann Arbor stages with high IPI. Malignant lymphomas of the thyroid gland are exceedingly rare, accounting for 2% of thyroid cancers, out of which the literature reveals a single case report of THRLBCL arising from the thyroid. THRLBCL represents an aggressive form of lymphoma and is treated according to stage-matched DLBCL, although the effects of Rituximab in this population is variable. Conclusion: Hashimoto’s is considered a risk for thyroid lymphoma usually diffuse large B-cell lymphoma and MALT lymphoma. We present a rare case of THRLBCL occurring in the setting of Hashimoto’s with acute thyroid gland enlargement.

Detailed Phenotypic Characterization of T-Cell Populations in Reactive, Normal and Follicular Lymphoma Nodes: Elevation of Follicular B Helper T-Cell Subsets in Follicular Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2948-2948
Author(s):  
Shannon P. Hilchey ◽  
Shelley Secor-Socha ◽  
Matthew R. Cochran ◽  
Ollivier Hyrien ◽  
W. Richard Burack ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Lymph Nodes ◽  
Follicular Lymphoma ◽  
B Cell ◽  
Critical Role ◽  
Pairwise Comparison ◽  
Cell Populations ◽  
Tfh Cells

Abstract Abstract 2948 Poster Board II-924 The tumor microenvironment of follicular lymphoma (FL) has been shown to play a critical role in the biology of this disease, and to be predictive of treatment outcome for FL patients. To gain further insight into the biology of the FL microenvironment, we asked whether differences exist between the T-cell populations within FL involved lymph nodes (FLN; n=13), as compared to that seen in either reactive (RLN; n= 10) or normal lymph nodes (NLN; n=11; obtained from patients undergoing vascular surgery whereby lymph nodes are removed to gain access to the vascular structures), using 11-color flow cytometry. Interestingly, the proportions of the T-cell populations shown in Table 1 were not statistically different between FLN and RLN, whereas they were statistically different between FLN and NLN. Specifically, the FLN demonstrate higher proportions of CD4+CD45RA−CCR7− T-effector memory cells (TEM) and lower proportions of both CD4+CD45RA−CCR7+ T-central memory (TCM) and CD4+CD45RA+ naïve T-cell populations, as compared to that of the NLN. In addition, within the FLN the TCM subpopulations demonstrate a higher proportion of CXCR5+ non-polarized T-cells as compared to the NLN. In contrast, when the proportions of the TEM subpopulations were examined, there were no significant differences between the FLN, RLN and NLN.TABLE 1CD8+ (%CD3+)CD4+ (%CD3+)Naïve (%CD4+)TCM (%CD4+)TEM (%CD4+)non-preTH1 (%TCM)non-polarized (%TCM)pre-TH1 (%TCM) FLN18.2±2.570.8±3.215.0±2.115.5±1.764.0±3.030.5±3.749.2±5.020.2±2.2 RLN14.4±2.879.9±3.423.6±5.215.0±2.452.6±5.839.8±3.435.4±3.224.3±3.2 NLN10.5±1.4*82.9±2.1*28.7±4.7*21.9±1.345.4±4.9*39.0±1.9*34.2±3.0*25.8±1.7Statistical analysis was performed using Wilcoxon rank sum tests (distribution free).*p<0.05, pairwise comparison (bold text). We next examined the proportion of the total CD45RA− memory CD4+ T-cells that were CXCR5+, a phenotype consistent with Follicular B Helper T-cells (TFH). Such TFH cells are crucial for the elicitation of B-cell memory and the generation of high affinity antibody responses. Whereas there was no significant difference in the mean percent of the memory T-cells that have a TFH phenotype in the FLN (64.1±5.0%) as compared to that seen in the RLN (55.8±4.6%), the proportion of TFH in the FLN was significantly higher than that seen in the NLN (48.0±4.0%). As discrete TFH populations have been identified based on their immunophenotype and anatomical localization, we next evaluated the distribution of TFH subpopulations, as defined by their surface expression of CD25 and CD57.TABLE 2Germinal Center (GC)Light zoneOuter zoneDual CD25+CD57+FLN16.4±5.022.5±2.754.4±4.16.72±1.06RLN9.4±0.5*15.5±3.272.9±3.6*2.21±0.50*NLN9.3±1.29.4±1.3*80.0±2.5*1.24±0.13*Statistical analysis was performed using Wilcoxon rank sum tests (distribution free).*p<0.05, pairwise comparison (bold text). In FLN there appears to be a skewing of TFH subsets away from the CD25−CD57− outer zone subset (a component of which is reported to contain pre-formed CD40L and thus likely provides help to GC-B cells) and towards the CD25+CD57− GC subset (reported to suppress TFH cell help to GC B-cells and inhibit AID expression); and towards the CD25−CD57+ light zone subset (reported to provide help to GC B-cells by inducing expression of AID, as well as inducing immunoglobulin production and class switching). Finally, we identified a potentially unique “dual” CD25+CD57+ population of TFH cells, with a higher frequency seen in FLN (6.72±1.06%) compared to both RLN (2.21±0.50) and NLN (1.24±0.13), with frequencies as high as 12% seen in some FLN samples. Taken together our findings suggest that; (a) the T-cell subset distribution of FL is overall similar to that of RLN but different than that of NLN suggesting that the FLN microenvironment is driven in part by the same immune reactivity and inflammatory signals as seen in RLN and; (b) FLN have a higher proportion of TFH cells then that of NLN, and a different profile of TFH subsets than in both RLN and NLN. Given the critical role that TFH cells play in normal GC-B cell biology, we speculate that differences in the TFH populations in FLN compared to that of RLN and NLN may in part regulate the malignant transformation and/or survival of FL B-cells. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The S1P-analog FTY720 differentially modulates T-cell homing via HEV: T-cell–expressed S1P1 amplifies integrin activation in peripheral lymph nodes but not in Peyer patches

Blood ◽  
2005 ◽  
Vol 106 (4) ◽  
pp. 1314-1322 ◽  
Author(s):  
Cornelia Halin ◽  
M. Lucila Scimone ◽  
Roberto Bonasio ◽  
Jean-Marc Gauguet ◽  
Thorsten R. Mempel ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Integrin Activation ◽  
High Endothelial Venules ◽  
Peripheral Lymph ◽  
Sphingosine 1 Phosphate ◽  
T Cell Homing ◽  
Prolonged Retention ◽  
Lymphocyte Egress

AbstractSphingosine-1-phosphate (S1P) and its receptor S1P1 control T-cell egress from thymus and secondary lymphoid organs (SLOs). To further define the role of S1P1 in lymphocyte trafficking, we performed adoptive transfer experiments and intravital microscopy (IVM) using both S1P1–/– lymphocytes and recipient wild-type (WT) mice treated with FTY720, an immunosuppressant that downmodulates S1P receptors. S1P1 deficiency and FTY720 caused rapid disappearance of T cells from blood, prolonged retention in SLOs, and accumulation in bone marrow, but did not alter interstitial T-cell motility in peripheral lymph nodes (PLNs) as assessed by multiphoton IVM. However, S1P1–/– lymphocytes displayed reduced short-term homing to PLNs due to attenuated integrin-mediated firm arrest in high endothelial venules (HEVs). By contrast, S1P1–/– T cells homed normally to Peyer patches (PPs), whereas S1P1–/– B cells had a marked defect in homing to PPs and arrested poorly in PP HEVs. Therefore, S1P1 not only controls lymphocyte egress from SLOs, but also facilitates in a tissue- and subset-specific fashion integrin activation during homing. Interestingly, FTY720 treatment enhanced accumulation of both S1P1 sufficient and S1P1–/– T cells in PPs by enhancing integrin-mediated arrest in HEVs. Thus, FTY720 exerts unique effects on T-cell traffic in PPs that are independent of T-cell–expressed S1P1.

scholarly journals Stepwise transmigration cascade of T and B cells through the perivascular channel in lymph node high endothelial venules

2020 ◽  
Author(s):  
Kibaek Choe ◽  
Jieun Moon ◽  
Soo Yun Lee ◽  
Eunjoo Song ◽  
Ju Hee Back ◽  
...  
Keyword(s):  
Cell Migration ◽  
T Cell ◽  
B Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Hot Spots ◽  
Dependent Manner ◽  
T And B Cells ◽  
High Endothelial Venules ◽  
T Cell Migration

AbstractHigh endothelial venules (HEVs) effectively recruit circulating lymphocytes from the blood to lymph nodes. HEVs have endothelial cells (ECs) and perivascular sheaths consisting of fibroblastic reticular cells (FRCs). Many studies have characterized the multiple steps of lymphocyte migration interacting with ECs at the luminal side of HEVs. However, post-luminal migration steps are not well elucidated. Herein, we performed intravital imaging to investigate post-luminal T and B cell migration, consisting of trans-EC migration, crawling in the perivascular channel (a narrow space between ECs and FRCs) and trans-FRC migration. The post-luminal migration of T cells occurred in a PNAd-dependent manner. Remarkably, we found hot spots for the trans-EC and trans-FRC migration of T and B cells. Interestingly, T and B cells preferentially shared trans-FRC migration hot spots but not trans-EC migration hot spots. Furthermore, the trans-FRC T cell migration was confined to fewer sites than trans-EC T cell migration, and trans-FRC migration of T and B cells preferentially occurred at FRCs covered by CD11c+ dendritic cells in HEVs. These results suggest that HEV ECs and FRCs with perivascular DCs delicately regulate T and B cell entry into lymph nodes.

scholarly journals Infection of B Cell Follicle-Resident Cells by Friend Retrovirus Occurs during Acute Infection and Is Maintained during Viral Persistence

mBio ◽  
2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Sonja Windmann ◽  
Lucas Otto ◽  
Camilla Patrizia Hrycak ◽  
Anna Malyshkina ◽  
Nadine Bongard ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Cell Population ◽  
Follicular Cells ◽  
Friend Retrovirus ◽  
Infected Cells ◽  
Cell Follicle

ABSTRACTB cell follicles of the spleen and lymph nodes are immune privileged sites and serve as sanctuaries for infected CD4+cells in HIV infection. It is assumed that CD8+T cell responses promote the establishment of the reservoir, as B cell follicles do not permit CD8+T cell entry. Here we analyzed the infected cell population in the Friend retrovirus (FV) infection and investigated whether FV can similarly infect follicular cells. For analysis of FV-infected cells, we constructed a recombinant FV encoding the bright fluorescent protein mWasabi and performed flow cytometry with cells isolated from spleens, lymph nodes and bone marrow of FV-mWasabi-infected mice. Using t-stochastic neighbor embedding for data exploration, we demonstrate how the target cell population changes during the course of infection. While FV was widely distributed in erythrocytes, myeloid cells, B cells, and CD4+T cells in the acute phase of infection, the bulk viral load in the late phase was carried by macrophages and follicular B and CD4+T cells, suggesting that FV persists in cells that are protected from CD8+T cell killing. Importantly, seeding into follicular cells was equally observed in CD8+T cell-depleted mice and in highly FV-susceptible mice that mount a very weak immune response, demonstrating that infection of follicular cells is not driven by immune pressure. Our data demonstrate that infection of cells in the B cell follicle is a characteristic of the FV infection, making this murine retrovirus an even more valuable model for development of retrovirus immunotherapy approaches.IMPORTANCEHuman immunodeficiency virus is notorious for its ability to avoid clearance by therapeutic interventions, which is partly attributed to the establishment of reservoirs in latently infected cells and cells that reside in immunologically privileged B cell follicles. In the work presented here, we show that cells of the B cell follicle are equally infected by a simple mouse gammaretrovirus. Using fluorescently labeled Friend retrovirus, we found that B cells and T cells in the B cell follicle, while not carrying the bulk of the virus load, were indeed infected by Friend virus in the early acute phase of the infection and persisted in the chronic infection. Our results suggest that infection of follicular cells may be a shared property of lymphotropic viruses and propose the FV infection of mice as a useful model to study strategies for follicular reservoir elimination.

scholarly journals Stepwise transmigration of T- and B cells through a perivascular channel in high endothelial venules

2021 ◽  
Vol 4 (8) ◽  
pp. e202101086
Author(s):  
Kibaek Choe ◽  
Jieun Moon ◽  
Soo Yun Lee ◽  
Eunjoo Song ◽  
Ju Hee Back ◽  
...  
Keyword(s):  
Cell Migration ◽  
T Cell ◽  
B Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Hot Spots ◽  
Dependent Manner ◽  
T And B Cells ◽  
High Endothelial Venules ◽  
T Cell Migration

High endothelial venules (HEVs) effectively recruit circulating lymphocytes from the blood to lymph nodes. HEVs have endothelial cells (ECs) and perivascular sheaths consisting of fibroblastic reticular cells (FRCs). Yet, post-luminal lymphocyte migration steps are not well elucidated. Herein, we performed intravital imaging to investigate post-luminal T- and B-cell migration in popliteal lymph node, consisting of trans-EC migration, crawling in the perivascular channel (a narrow space between ECs and FRCs) and trans-FRC migration. The post-luminal migration of T cells occurred in a PNAd-dependent manner. Remarkably, we found hot spots for the trans-EC and trans-FRC migration of T- and B cells. Interestingly, T- and B cells preferentially shared trans-FRC migration hot spots but not trans-EC migration hot spots. Furthermore, the trans-FRC T-cell migration was confined to fewer sites than trans-EC T-cell migration, and trans-FRC migration of T- and B cells preferentially occurred at FRCs covered by CD11c+ dendritic cells in HEVs. These results suggest that HEV ECs and FRCs with perivascular DCs delicately regulate T- and B-cell entry into peripheral lymph nodes.

scholarly journals B cell depletion impairs vaccination-induced CD8+ T cell responses in a type I interferon-dependent manner

2021 ◽  
pp. annrheumdis-2021-220435
Author(s):  
Theresa Graalmann ◽  
Katharina Borst ◽  
Himanshu Manchanda ◽  
Lea Vaas ◽  
Matthias Bruhn ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Expansion ◽  
De Novo ◽  
T Cell Responses ◽  
Type I ◽  
Cell Responses ◽  
T Cell Expansion

ObjectivesThe monoclonal anti-CD20 antibody rituximab is frequently applied in the treatment of lymphoma as well as autoimmune diseases and confers efficient depletion of recirculating B cells. Correspondingly, B cell-depleted patients barely mount de novo antibody responses during infections or vaccinations. Therefore, efficient immune responses of B cell-depleted patients largely depend on protective T cell responses.MethodsCD8+ T cell expansion was studied in rituximab-treated rheumatoid arthritis (RA) patients and B cell-deficient mice on vaccination/infection with different vaccines/pathogens.ResultsRituximab-treated RA patients vaccinated with Influvac showed reduced expansion of influenza-specific CD8+ T cells when compared with healthy controls. Moreover, B cell-deficient JHT mice infected with mouse-adapted Influenza or modified vaccinia virus Ankara showed less vigorous expansion of virus-specific CD8+ T cells than wild type mice. Of note, JHT mice do not have an intrinsic impairment of CD8+ T cell expansion, since infection with vaccinia virus induced similar T cell expansion in JHT and wild type mice. Direct type I interferon receptor signalling of B cells was necessary to induce several chemokines in B cells and to support T cell help by enhancing the expression of MHC-I.ConclusionsDepending on the stimulus, B cells can modulate CD8+ T cell responses. Thus, B cell depletion causes a deficiency of de novo antibody responses and affects the efficacy of cellular response including cytotoxic T cells. The choice of the appropriate vaccine to vaccinate B cell-depleted patients has to be re-evaluated in order to efficiently induce protective CD8+ T cell responses.

scholarly journals Disproportion in T-cell subpopulations in immunodeficient mutant hr/hr mice.

1979 ◽  
Vol 149 (1) ◽  
pp. 228-233 ◽  
Author(s):  
A B Reske-Kunz ◽  
M P Scheid ◽  
E A Boyse
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Lymph Nodes ◽  
Salient Feature ◽  
Mutant Gene ◽  
Cell Subpopulations ◽  
T Cell Subpopulations

Mice of the HRS strain, which carry the mutant gene hr, were examined for abnormalities in representation of the three T-cell sets Ly1, Ly23, and Ly123 in the spleen. The salient feature of hr/hr mice, which are immunologically deficient, in comparison with +/hr segregants, was a gross disproportion in numbers of cells belonging to the Ly1 and Ly123 sets, at the age of 3--3.5 mo. At this age, Ly123 cells of hr/hr spleen outnumbered Ly1 cells by 2:1, whereas in +/hr spleens Ly123 cells were outnumbered by approximately 1:2. Cells from pooled lymph nodes of hr/hr mice did not show a correspondingly gross disporprotion of Ly1 and Ly123 cells. Total counts of splenic T cells, and of B cells, were not significantly different in hr/hr and +/hr mice.

scholarly journals The role of H-2-linked genes in helper T cell function. VII. Expression of I region and immune response genes by B cells in bystander help assays.

1980 ◽  
Vol 152 (5) ◽  
pp. 1274-1288 ◽  
Author(s):  
P Marrack ◽  
J W Kappler
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Function ◽  
High Responder ◽  
Helper T Cells ◽  
Spleen Cells ◽  
Region Gene ◽  
Immunoglobulin Receptor

The mode of action by bystander helper T cells was investigated by priming (responder X nonresponder) (B6A)F1 T cells with poly-L-(Tyr, Glu)-poly-D,L-Ala--poly-L-Lys [(TG)-A--L] and titrating the ability of these cells to stimulate an anti-sheep red blood cell (SRBC) response of parental B cells and macrophages in the presence of (TG)-A--L. Under limiting T cell conditions, and in the presence of (TG)-A--L, (TG)-A--L-responsive T cells were able to drive anti-SRBC responses of high-responder C57BL/10.SgSn (B10) B cells and macrophages (M0), but not of low-responder (B10.A) B cells and M0. Surprisingly, the (TG)-A--L-driven anti-SRBC response of B10.A B cells was not restored by addition of high-responder acessory cells, in the form of (B6A)F1 peritoneal or irradiated T cell-depleted spleen cells, or in the form of B10 nonirradiated T cell-depleted spleen cells. These results suggested that (TG)-A--L-specific Ir genes expressed by B cells controlled the ability of these cells to be induced to respond to SRBC by (TG)-A--L-responding T cells, implying that direct contact between the SRBC-binding B cell precursor and the (TG)-A--L-responsive helper T cells was required. Analogous results were obtained for keyhold limpet hemocyanin (KLH)-driven bystander help using KLH-primed F1 T cells restricted to interact with cells on only one of the parental haplotypes by maturing them in parental bone marrow chimeras. It was hypothesized that bystander help was mediated by nonspecific uptake of antigen [(TG)-A--L or KLH] by SRBC-specific b cells and subsequent display of the antigen on the B cell surface in association with Ir of I-region gene products, in a fashion similar to the M0, where it was then recognized by helper T cells. Such an explanation was supported by the observation that high concentrations of antigen were required to elicit bystander help. This hypothesis raises the possibility of B cell processing of antigen bound to its immunoglobulin receptor and subsequent presentation of antigen to helper T cells.

scholarly journals Early Reconstitution of Antibody Secreting Cells after Allogeneic Stem Cell Transplantation

2022 ◽  
Vol 11 (1) ◽  
pp. 270
Author(s):  
Martina Hinterleitner ◽  
Clemens Hinterleitner ◽  
Elke Malenke ◽  
Birgit Federmann ◽  
Ursula Holzer ◽  
...  
Keyword(s):  
Innate Immunity ◽  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
B Cells ◽  
Stem Cell Transplantation ◽  
B Cell ◽  
Cell Transplantation ◽  
Antibody Secreting Cells

Immune cell reconstitution after stem cell transplantation is allocated over several stages. Whereas cells mediating innate immunity recover rapidly, adaptive immune cells, including T and B cells, recover slowly over several months. In this study we investigated kinetics and reconstitution of de novo B cell formation in patients receiving CD3 and CD19 depleted haploidentical stem cell transplantation with additional in vivo T cell depletion with monoclonal anti-CD3 antibody. This model enables a detailed in vivo evaluation of hierarchy and attribution of defined lymphocyte populations without skewing by mTOR- or NFAT-inhibitors. As expected CD3+ T cells and their subsets had delayed reconstitution (<100 cells/μL at day +90). Well defined CD19+ B lymphocytes of naïve and memory phenotype were detected at day +60. Remarkably, we observed a very early reconstitution of antibody-secreting cells (ASC) at day +14. These ASC carried the HLA-haplotype of the donor and secreted the isotypes IgM and IgA more prevalent than IgG. They correlated with a population of CD19− CD27− CD38low/+ CD138− cells. Of note, reconstitution of this ASC occurred without detectable circulating T cells and before increase of BAFF or other B cell stimulating factors. In summary, we describe a rapid reconstitution of peripheral blood ASC after CD3 and CD19 depleted haploidentical stem cell transplantation, far preceding detection of naïve and memory type B cells. Incidence before T cell reconstitution and spontaneous secretion of immunoglobulins allocate these early ASC to innate immunity, eventually maintaining natural antibody levels.

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