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Results for “Marginal zone B cells”

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PubMed2001

A novel recurrent translocation t(11;14)(p11;q32) in splenic marginal zone B cell lymphoma.

A novel recurrent translocation t(11;14)(p11;q32) was found in three patients with splenic marginal zone B cell lymphoma (MZBCL). Fluorescence in situ hybridization (FISH) studies with IgH probes revealed in all cases involvement of the IgH locus, with breakpoint downstream of the IGVH sequences. Partner genes at 11p11 were not identified. The translocation defined the stem line in two patients, who carried additional cytogenetic aberrations, including a 17p deletion, present in both cases. In one patient a 7q- chromosome was the primary cytogenetic defect, the t(11;14) having been found in four out of 11 abnormal metaphase cells at the time of transformation into high-grade MZBCL. Hematological features in all cases included splenomegaly with peripheral blood (PB) involvement by a monoclonal B cell population consisting of lymphocytes with villous projections and several blast-like cells. The immunophenotype was CD19+; CD22bright+; CD23-, CD10-, CD5-, surface Igbright+. A bone biopsy in one patient revealed an interstitial infiltration with an intrasinusoidal pattern of growth. Histological studies on spleen specimens in two patients showed an expanded marginal zone, with small lymphocytes and several blast-like cells. One patient had a therapy-demanding disease, with partial, short-term responses to cytotoxic treatment; one patient transformed into a high-grade MZBCL involving the gut, the PB and the bone marrow 2 years after diagnosis; one patient was unresponsive to cytotoxic treatment and underwent splenectomy. The t(11;14)(p11;q32) may define a subset of splenic MZBCL with a high-grade component and a relatively aggressive clinical behavior.

Aged↗
PubMed2006

Evidence that marginal zone B cells possess an enhanced secretory apparatus and exhibit superior secretory activity.

Marginal zone B (MZB) cells are the first splenic B cells to initiate Ab secretion against polysaccharide-encapsulated Ags in vivo. This swift MZB cell response can be reproduced in vitro as LPS treatment induces Ab secretion in as little as 12 h. Conversely, in vitro LPS treatment of splenic follicular B (FOB) cells results in Ab secretion after 2-3 days. The basis for these distinct response kinetics is not understood. We performed ex vivo analysis of resting and LPS-stimulated murine MZB and FOB cells and found that MZB cells express higher levels of the LPS TLR complex RP105/MD-1 and respond to much lower concentrations of LPS than do FOB cells. Furthermore, increasing doses of LPS do not accelerate the kinetics by which FOB cells transition into Ab secretion. Ultrastructural analysis of resting cells demonstrated that rough endoplasmic reticulum is more abundant in MZB cells than in FOB cells. Additionally, RT-PCR and immunoblot analyses revealed that numerous endoplasmic reticulum resident chaperones and folding enzymes are expressed at greater levels in resting MZB cells than in resting FOB cells. Although both LPS-stimulated MZB and FOB cells increase expression of these factors, MZB cells exhibit a more rapid increase that correlates with accelerated kinetics of Ab secretion and higher per cell output of secreted IgM. These data indicate that MZB cells are equipped for exquisite sensitivity to bacterial components like LPS and poised for rapid, robust Ab production, making MZB cells ideally suited as frontline defenders in humoral immunity.

Animals↗
PubMed2001

Marginal zone B cell lymphomas of Waldeyer's ring--a report of two tonsillectomy cases resembling histomorphological features of inflammatory lesions.

We identified two cases of lymphoma of the mucosa-associated lymphoid tissue (MALT) type in 11 tonsillectomy specimens of primary B cell lymphoma of Waldeyer's ring. Both patients were Japanese females presenting with bilateral enlargement of the palatine tonsils. One had a history of chronic otitis media. In that case, the lesion was characterized by an extrafollicular growth pattern with marginal zone-like arrangement. The tumor was mainly composed of medium-sized cells with round or indented nuclei with scant cytoplasm (centrocyte-like cells). In the other patient, most tumor cells were mature plasma cells, plasmacytoid cells, proplasmacytes, and immunoblasts with scattered centrocyte-like cells. Tropism of tumor cells for the epithelium was noted in both lesions. Primary marginal zone B cell lymphoma of the MALT type arising from Waldeyer's ring has rarely been reported in the literature, causing certain diagnostic problems. Various florid reactive lymphoproliferative disorders, including chronic tonsillitis and infectious mononucleosis, should be differentiated from this type of primary Waldeyer's ring lymphoma.

Adult↗
PubMed1997

Marginal zone B cells exhibit unique activation, proliferative and immunoglobulin secretory responses.

Mouse splenic B cells can be separated based on their distinctive expression of cell surface antigens. Marginal zone (MZ) B cells are CD38high CD21high CD23low/-, while follicular (FO) B cells are CD21int CD23int and newly formed (NF) B cells are CD21dim/- CD23-. Exploiting these phenotypic distinctions, we isolated the three B cell subsets and assessed their other phenotypic differences and functional capabilities in vitro. FO B cells proliferate more than the other B cell subsets in response to either IgM or CD38 cross-linking. MZ B cells proliferate better than FO B cells when stimulated with lipopolysaccharide (LPS), sub-optimal levels of LPS and CD38 cross-linking or CD40 ligation. When NF, FO and MZ B cells were stimulated with either LPS or LPS and interleukin-4, MZ B cells secreted more IgM and IgG3 than the other two subsets. Similarly, calcium fluxes measured within MZ B cells are larger in amplitude and more sustained after B cell receptor cross-linking than those found in the other two subsets. Collectively, these results indicate that CD38high CD21high CD23low/- MZ B cells are specially suited to play a unique role in response to antigens delivered to the MZ area.

Animals↗
PubMed2001

Development of early gastric cancer 4 and 5 years after complete remission of Helicobacter pylori associated gastric low grade marginal zone B cell lymphoma of MALT type.

AIM: To report 3 of 120 patients on the German MALT lymphoma trial with H. pylori associated gastric MALT lymphoma who developed early gastric cancer 4 and 5 years, after complete lymphoma remission following cure of H. pylori infection. PATIENTS AND RESULTS: Three patients (two men, 74 and 70 years; one women, 77 years) with H. pylori-associated low-grade MALT lymphoma achieved complete lymphoma remission after being cured. Surveillance endoscopies were performed twice a year in accordance to the protocol. Four years after complete lymphoma remission in two patients, and after 5 years in the other, early gastric adenocarcinoma of the mucosa-type, type IIa and type IIc, respectively, was detected, which were completely removed by endoscopic mucosa resection. In one patient, the gastric cancer was diagnosed at the same location as the previous MALT lymphoma, in the other patients it was detected at different sites of the stomach distant from location of the previous MALT lymphoma. The patients were H. pylori negative during the whole follow-up time. CONCLUSION: These findings strengthen the importance of regular Long-term follow-up endoscopies in patients with complete remission of gastric MALT lymphoma after cure of H. pylori infection. Furthermore, gastric adenocarcinoma may develop despite eradication of H. pylori.

Adenocarcinoma↗
PubMed2005

Altered migration, recruitment, and somatic hypermutation in the early response of marginal zone B cells to T cell-dependent antigen.

The early responses of follicular (Fo) and marginal zone (MZ) B cells to T cell-dependent Ag were compared using anti-hen egg lysozyme (HEL+) B cells capable of class switch recombination and somatic hypermutation (SHM). Purified CD21/(35int)CD23high Fo and CD21/35(high)CD23low MZ splenic B cells from SW(HEL) Ig-transgenic mice were transferred into wild-type recipients and challenged with HEL-sheep RBC. Responding HEL+ B cells from both populations switched efficiently to IgG1, generated syndecan-1+ Ab-secreting cells, and exhibited equivalent rates of proliferation. However, the expansion of HEL+ MZ B cells lagged significantly behind that of HEL+ Fo B cells due to less efficient homing to the outer periarteriolar lymphatic sheath and reduced recruitment into the proliferative response. Despite the equivalent rates of class switch recombination, the onset of SHM was delayed in the MZ subset, indicating that these two activation-induced cytidine deaminase-dependent events are uncoupled in the early response of MZ B cells. Migration of HEL+ B cells into germinal centers coincided with the onset of SHM, occurring more rapidly with Fo vs MZ responders. These results are consistent with the concept that Fo and MZ B cells have evolved to specialize in T cell-dependent and T-independent responses respectively.

Animals↗
PubMed1996

Marginal zone B cell lymphoma of the parotid glands: results of a randomised trial comparing radiotherapy to combined therapy.

39 patients with marginal zone B cell lymphoma (MZBCL) of the parotid glands (stages I or II) were studied. They were randomized to be treated with either radiotherapy alone (extended fields, 4500 cGy) or radiotherapy (the same schedule) plus adjuvant chemotherapy (cyclophosphamide, vincristine and prednisone). The end points were survival and time to treatment failure (TTF). Patients who received radiotherapy alone had a complete remission rate of 100%, the TTF was 90% at 5 years and overall survival at 5 years was 90% with no statistical difference when compared with patients who received combined therapy [100, 80 and 95%, respectively (P = 0.5)]. Although adjuvant chemotherapy was well tolerated, the use of this therapeutic approach in patients with early stage MZBCL did not offer any advantage over radiotherapy alone as the initial treatment. Until now, radiotherapy was considered the treatment of choice in this clinical setting of patients.

Adult↗
PubMed2002

Extranodal marginal zone B cell lymphoma of MALT type involving the mucosa of both the urinary bladder and stomach.

Primary lymphoma of the urinary bladder is a very rare tumour. A bladder tumour was found in a 57 year old man with obstructive dysuria. It was found by histological and immunohistohistochemical investigation to be an extranodal marginal zone B cell lymphoma. Lymphoepithelial lesions were absent, but were found in a clinically silent gastric lymphoma discovered four weeks later during staging investigations; this gastric lymphoma was negative for Helicobacter pylori by breath test and molecular biological analysis. Sequencing of the clonal immunoglobulin heavy chain gene in both tumours indicated the same precursor cell, of follicular or post follicular origin. In synopsis, the data suggested that this was a case of primary lymphoma of the bladder with involvement of the stomach. The application of a chromosome 3 specific alpha satellite probe revealed trisomy 3. A tumour with these characteristics arising as a lymphoma of the bladder with a metachronous involvement of the gastric mucosa has not been described previously.

Humans↗
PubMed2005

Accumulation of marginal zone B cells and accelerated loss of follicular dendritic cells in NF-kappaB p50-deficient mice.

BACKGROUND: Marginal zone (MZ) B cells play important roles in the early phases of humoral immune responses. In addition to possessing an inherent capacity to rapidly differentiate into antibody secreting cells, MZ B cells also help to regulate the fate of both T-independent and T-dependent blood-borne antigens in the spleen. For T-dependent antigens, MZ B cells bind IgM-antigen complexes in a complement-dependent manner. Once MZ B cells bind IgM-containing immune complexes (IgM-IC), they transport them into B cell follicles for deposition onto follicular dendritic cells (FDCs), an important component of secreted IgM's ability to enhance adaptive immune responses. To further define the requirement for MZ B cells in IgM-IC deposition, mice deficient in the NF-kappaB protein p50, which have been reported to lack MZ B cells, were analyzed for their ability to trap IgM-IC onto FDCs. RESULTS: Mice (2 months of age) deficient in p50 (p50-/-) had small numbers of MZ B cells, as determined by cell surface phenotype and localization in the splenic MZ. These cells bound high levels of IgM-IC both in vivo and in vitro. Subsequent to the binding of IgM-IC by the MZ B cells in p50-/- mice, small amounts of IgM-IC were found localized on FDCs, suggesting that the MZ B cells retained their ability to transport these complexes into splenic follicles. Strikingly, MZ B cells accumulated with age in p50-/- mice. By 6 months of age, p50-/- mice contained normal numbers of these cells as defined by CD21/CD23 profile and high level expression of CD1d, CD9, and IgM, and by their positioning around the marginal sinus. However, FDCs from these older p50-/- mice exhibited a reduced capacity to trap IgM-IC and retain complement components. CONCLUSION: These results demonstrate that while the p50 component of the NF-kappaB transcription complex plays an important role in the early development of MZ B cells, MZ B cells can develop and accumulate in mice lacking this protein. These results highlight the interface between genetic deficiencies and age, and suggest that different transcription factors may play distinct roles in the development and maintenance of cell populations at different ages.

Aging↗
PubMed1989

Human marginal zone B cells are not an activated B cell subset: strong expression of CD21 as a putative mediator for rapid B cell activation.

In the human spleen the marginal zone (MZ) contains medium-sized B cells with a distinct immunophenotype. A main function attributed to the MZ is its involvement in the primary response to blood-borne antigens, in particular to thymus-independent antigens type 2. In this study the presence of antigens related to activation and proliferation was evaluated in human spleens by immunohistochemical staining. It appeared that MZ B cells do not show interleukin 2 receptor expression, and are in G0 phase of the cell cycle, as demonstrated by the lack of Ki-67 reactivity. The most interesting finding is the high CD21 expression by MZ B cells in the absence of IgD expression. As the CD21 antigen has been shown to be involved in B cell activation in close linkage with IgM, it can be suggested that MZ B cells are particularly well equipped for rapid and easy activation in a primary immune response.

Antigens, CD↗
PubMed2002

Extranodal marginal zone B cell lymphomas of the uvea: an analysis of 13 cases.

The majority of primary lymphoproliferative lesions of the uvea represent low-grade B cell lymphomas and often display a prominent plasmacellular differentiation. The purpose of the current study was to classify the uveal lymphoproliferations according to the REAL classification; examine the immune profile of the plasmacellular differentiated tumour cells using the plasma cell-related antigens multiple myeloma oncogene-1-protein (MUM1), Vs38c, CD38 and CD138; and to compare this profile with that of mature reactive plasma cells. Following fixation, 13 lymphoproliferative lesions of the uvea were categorized on the basis of their morphology and immunophenotype according to the REAL classification. Included in the immunohistochemistry were B cell-specific activator protein (BSAP), MUM1, Vs38c, CD38 and CD138. Nested polymerase chain reaction (PCR) was also performed on DNA extracted from paraffin sections for the detection of gene rearrangements of the heavy immunoglobulin chain (IgH). All of the 13 uveal tract lymphoproliferative lesions represented malignant lymphoma of B cell non-Hodgkin type and could be diagnosed as 'extranodal marginal zone B cell lymphomas' (EMZL). The degree of plasmacellular differentiation varied between the tumours. In contrast to their non-plasmacytoid counterparts, the 'plasmacytoid' EMZL tumour cells were negative for the B cell markers CD20 and BSAP, and demonstrated heterogeneous positivity for the markers MUM1, Vs38c, CD38 and CD138. The most consistent marker was MUM1, being observed in all tumours. Co-expression of all plasma cell markers was observed in four (31%) uveal EMZL. Loss of CD138 expression was observed in six (46%) tumours, of Vs38c expression in five (38%) and of CD38 in one (7%) tumour. Although the diagnosis of malignant lymphoma was unequivocally based on morphological and immunophenotypical features, the molecular analysis was able to demonstrate clonal B cell populations in only one uveal EMZL. All uveal lymphoid proliferations investigated represented EMZL, with the corresponding morphology and immunophenotype as seen in EMZL in other extranodal locations. MUM1, followed by CD38 expression, were the most constant plasma cell antigens in the plasmacytoid EMZL tumour cells, with both Vs38c and CD138 positivity being lost in many tumours. Aberrant immune profiles of plasma cell-related antigens may be of help in the establishment of malignancy in uveal lymphoproliferative lesions, particularly where interpretation of light chain expression and/or PCR results is difficult.

ADP-ribosyl Cyclase↗
PubMed2003

Low grade marginal zone B cell lymphoma of the breast associated with localised amyloidosis and corpora amylacea in a woman with long standing primary Sjögren's syndrome.

Primary low grade marginal zone B cell lymphoma (MZL) of the breast and localised mammary amyloidosis are exceedingly rare entities. This report describes the case of a woman with long standing Sjögren's syndrome presenting with asymptomatic MZL of the breast showing plasmacytic differentiation, associated with local ductular amyloidosis. The lesion was discovered incidentally in breast tissue resected for microcalcifications. Immunohistochemistry revealed kappa light chain restriction, supporting the neoplastic nature of the infiltrate. A retrospective molecular study of the salivary gland biopsy showed a B cell clone. This is the first report of the association of human mammary ductular amyloidosis with cartwheel shaped material identical to corpora amylacea, usually seen in brain, lung, and prostate, but unknown in the human breast. The excellent outcome without treatment seen in this patient further emphasises the need to distinguish between MZL with plasmacytic differentiation and extramedullary plasmacytoma.

Adult↗
PubMed2001

Recirculating and marginal zone B cell populations can be established and maintained independently of primary and secondary follicles.

In normal spleen, most recirculating naïve IgM+IgDhi B cells are located within primary follicles and mantle zones of secondary follicles. By contrast, the marginal zone contains a heterogeneous population of IgMhiIgDlo/- B cells that are mostly non-recirculating. Although these are dynamic populations they are maintained at a constant size, the fundamental homeostatic mechanisms remain uncertain. One possibility is that the presence and turnover of each of the B cell populations is dependent on their location within discrete splenic compartments. To investigate this, we have characterized immature, non-recirculating, mature recirculating, marginal zone and B-1 cell populations in TNF-/- and TNF/lymphotoxin(LT)-alpha-/- mice that have disorganized splenic architecture. Labelling with 5-bromo-2'-deoxyuridine revealed that turnover of B cells in TNF-/- mice is normal, but is diminished in TNF/LT-alpha-/- mice. The recirculating B cell populations in both mutant strains are normal in proportion and phenotype. Marginal zone B cells are not seen in TNF/LT-alpha-/- mice, but this population appears normal in TNF-/- mice, even though they lack germinal centres. These findings indicate that peripheral B cell subsets can be established and maintained independently of normal follicular architecture.

Animals↗
PubMed2002

Marginal zone B cells in neonatal rats express intermediate levels of CD90 (Thy-1).

Here we show that marginal zone (MZ)-B cells in rats can already be detected in neonatal spleen from two days after birth. At this time point, morphologically distinct MZs are not present yet and the vast majority of B cells in spleen are located in a concentric area surrounding the T cell zones (PALS). Before MZs are obviously detectable in spleen (14 days after birth), MZ-B cells seem to be enriched at the outer zones of the concentric B cell areas. Similar to adult rats, neonatal MZ-B cells are intermediate-sized cells that express high levels of surface (s)IgM and HIS57 antigen, and low levels of sIgD and CD45R (HIS24). We show here, however, that in contrast to adult MZ-B cells, MZ-B cells (and also recirculating follicular (RF)-B cells) in neonatal rats express higher levels of CD90 (Thy-1). In adult rats, expression of CD90 on the B cell lineage is confined to immature B cells. We speculate that the expression of CD90 on neonatal MZ-B cells may have implications for their responsiveness to polysaccharide (T cell-independent type 2) antigens.

Animals↗
PubMed2006

Dissemination of a Sjögren's syndrome-associated extranodal marginal-zone B cell lymphoma: circulating lymphoma cells and invariant mutation pattern of nodal Ig heavy- and light-chain variable-region gene rearrangements.

OBJECTIVE: Both the genesis and outgrowth of extranodal marginal-zone B cell lymphomas (MZLs) of the mucosa-associated lymphoid tissue (MALT) type are generally thought to represent antigen-driven processes. We undertook this study to analyze lymphoma progression and dissemination outside of the MALT-type lesions. METHODS: Histopathologic and Ig heavy- and light-chain variable-region gene (V(H/L)) analyses were performed in sequential tissue samples from a patient with primary Sjögren's syndrome (SS) with glandular (parotid) manifestations and subsequent nodal dissemination of a low-grade MZL. RESULTS: This MZL expressed a CD20+,CD27+,sIgM/kappa+,IgD-,CD5-,CD10-,Bcl-6-,CD23-,p53-,p21-,MDM2- phenotype and mutated V(H)1-69/D2-21/J(H)4alpha-V(kappa)A27/J(kappa)2 Ig rearrangements. Notably, circulating lymphoma cells from the parotid glands occurred transiently in the patient's blood, as detected by single-cell polymerase chain reaction. In addition, 2 minor B cell clones (clones 2 and 3, with V(H)3-07/D3-22/J(H)3b-V(lambda)3L/J(lambda)2/3 and V(H)3-64/D3-03/J(H)2-V(kappa)A19/J(kappa)2 rearrangements, respectively) were also detected in the parotid glands and blood, and 1 of these (clone 2) was also detected in the lymph nodes. Ig V(H/L) analyses revealed ongoing (antigen-driven) mutations of the glandular lymphoma rearrangements, but an invariant mutation pattern of their nodal counterparts. CONCLUSION: These data indicate coexpansion and transient (re)circulation of the lymphoma clone and 2 additional glandular B cell clones in a primary SS-associated extranodal MZL. Combined histologic and molecular features of the nodal lymphoma subclone reflect a process of "follicular colonization" that eventually froze the mutation machinery after accumulation of additional (antigen-driven) Ig V(H/L) mutations.

Female↗
PubMed2005

TLR-9 activation of marginal zone B cells in lupus mice regulates immunity through increased IL-10 production.

Bacterial DNA triggers B-cell proliferation and induces immunoglobulin secretion. Chromatin-IgG complexes activate autoreactive B cells by co-engaging B-cell receptor (BCR) and TLR-9, thus suggesting a role for innate signaling in systemic autoimmunity. Spleen cells from lupus prone Palmerston North (PN) mice produce several fold less IL-12p40 than controls in response to CpG-oligodeoxynucleotides (ODNs). Here we show that B cells are primarily responsible for this abnormality. The removal of B cells from PN cultures markedly increased IL-12p40. Moreover, the addition of purified B cells back to PN splenocyte cultures resulted in a B-cell number dependent/ IL-10-mediated suppression of IL-12p40. The B cells were the major source of IL-10. In response to CpG, B cells from several lupus strains produced twice as a much IL-10 as controls, but failed to produce IL-10 when stimulated through BCR or CD40. PN and control mice expressed IL-10R similarly, and the difference in IL-10 secretion remained when anti-IL-10R blocking antibodies were used. IFN-gamma and IL-4 regulated CpG-induced IL-10 secretion in opposite directions. The abnormal IL-10 response in lupus mice was derived from B cells with the marginal zone phenotype, and could be downregulated with inhibitory ODNs. We hypothesize that TLR-9 activated lupus B cells can modulate T-cell mediated inflammatory responses through IL-10 production. Therefore, B cells may contribute to the lupus pathogenesis in many different ways: as antigen-presenting cells for self antigens, as effector cells for autoantibody production, and as IL-10 secreting regulatory cells.

Animals↗
PubMed2006

Infection-associated lymphomas derived from marginal zone B cells: a model of antigen-driven lymphoproliferation.

Non-Hodgkin lymphomas develop from nodal and extranodal lymphoid tissues. A distinct subset of extranodal lymphomas arising from B cells of the marginal zone (MZ) of mucosa-associated lymphoid tissue (MALT) or spleen has been individualized. Growing evidence indicates that MZ lymphomas are associated with chronic antigenic stimulation by microbial pathogens and/or autoantigens. The list of microbial species associated with MZ lymphoproliferations has grown longer with molecular investigations and now comprises at least 5 distinct members: H. pylori, C. jejuni, B. burgdorferi, C. psittaci, and hepatitis C virus (HCV), which have been associated with gastric lymphoma, immunoproliferative small intestinal disease, cutaneous lymphoma, ocular lymphoma, and spleen lymphoma, respectively. A pathophysiologic scenario involving chronic and sustained stimulation of the immune system leading to lymphoid transformation has emerged. It defines a distinct category of infection-associated lymphoid malignancies, in which the infectious agent does not directly infect and transform lymphoid cells, as do the lymphotropic oncogenic viruses Epstein-Barr virus (EBV), human herpesvirus 8 (HHV8), and human T-lymphotropic virus 1 (HTLV-1), but rather indirectly increases the probability of lymphoid transformation by chronically stimulating the immune system to maintain a protracted proliferative state.

Antigen Presentation↗
PubMed2005

Activation of marginal zone B cells from lupus mice with type A(D) CpG-oligodeoxynucleotides.

Several types of CpG-oligodeoxynucleotides (ODN) have been recently characterized. In mice, type A(D) CpG-ODNs primarily stimulate macrophages and dendritic cells, but fail to stimulate B cells. On the contrary, type B(K) CpG-ODNs are excellent B cell activators. Type C CpG-ODNs combine features of both types A(D) and B(K) CpG-ODNs. Despite cell type preferences, all CpG-ODNs require the presence of TLR9 for activation. In this study, we show that a subset of B cells from lupus mice responds to type A(D) CpG-ODN stimulation vigorously and directly with increased CD25 and CD86 expression and IL-10 secretion. Furthermore, these CpG-ODNs induce high surface IgM expression and promote 50- to 100-fold higher IgM and IgG3 secretion in lupus B cells than in controls. This response is similar to that seen with bacterial DNA stimulation of B cells. Type A(D)-responsive cells are enriched within lupus B cells with the marginal zone (MZ) phenotype. These cells are at least twice more numerous in lupus mice than in controls. The ability of lupus B cells to respond to type A(D) CpG-ODN stimulation is not due to differential TLR9 expression. Therefore, type A(D) CpG-ODNs may contribute to the lupus pathogenesis by inducing MZ-B cell activation, costimulatory molecule expression, and polyclonal Ig secretion. Through increased IL-10 secretion, MZ-B cells may also modify the activity of other cell types, particularly dendritic cells and macrophages.

Adjuvants, Immunologic↗