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F G Kroese

Publications and source records attributed to F G Kroese.

At least 19 recordsLinked to original sources
PubMed2001

CD27 expression in the human splenic marginal zone: the infant marginal zone is populated by naive B cells.

The splenic marginal zone of adult humans contains B cells, of which most express CD27, an antigen only recently identified as a marker for somatically mutated memory B cells. We investigated whether and to which extent the developing marginal zone in infants and children is populated by either memory (CD27+) or naive (CD27-) B cells. Frozen sections of 32 spleens of infants and children ranging in age from 6 days to 15 years and 6 adult spleens were investigated. The expression of CD27 in combination with monoclonal antibodies against CD3, CD21, IgM, IgD and ASM-1 was analyzed by immunohistochemistry. The marginal zone was already present at 4 months after birth but CD21 expression was observed first after 2 years. CD27-positive marginal zone B cells were observed firstly 2 years after birth and increased in number to adult levels at the age of 5 years. We demonstrated that the MZ of infants and young children is populated by naive B cells, which are replaced by memory B cells in a time frame of 2 to 5 years. Before the age of 2 years, although present, memory B cells appear to be unable to colonize the marginal zone. Because of the absence of memory B cells in the marginal zone, the immune system of a child is not capable to initiate a rapid secondary humoral immune response comparable to the adult immune response.

Adolescent↗
PubMed2001

Slow recovery of follicular B cells and marginal zone B cells after chemotherapy: implications for humoral immunity.

Although most chemotherapeutic agents are known to cause primarily reduction or suppression of immune responses, surprisingly little is known about the influence of cytostatic agents on lymphoid tissue compartments such as the splenic marginal zone. The marginal zone plays an important role in the defence against encapsulated bacteria, which are potential candidates for postchemotherapeutic infections. We studied the effect of three different cytostatic agents (cisplatin, methotrexate, and cyclophosphamide) on B cell subpopulations in a rat model. Rats received a single dose of a single cytostatic agent and were sacrificed at different time points after treatment. Bone marrow, blood, mesenteric lymph nodes and spleens were analysed by flow-cytometry and immunohistochemistry. All three cytostatic agents showed severe bone marrow depression. CP and MTX showed only mild reduction of cell populations in the spleen. CyPh showed a severe reduction of recirculating follicular B (RF-B) cells and marginal zone B (MZ-B) cells. At day 24 most populations were already recovered, but RF-B cells and MZ-B cells were still reduced. The reduction of the marginal zone and late recovery may imply that, beside the overall increased infection risk due to neutropenia, patients treated with chemotherapy are at risk for developing infections from encapsulated bacteria for a considerable period of time after treatment, extending beyond the period of bone marrow depression.

Animals↗
PubMed2001

Immunoglobulin VH-gene usage of autoantibodies in mercuric chloride-induced membranous glomerulopathy in the rat.

Brown-Norway (BN) and Dorus Zadel Black (DZB) rats develop a T-cell-dependent membranous glomerulopathy (MGP) with high proteinuria and antiglomerular basement membrane (GBM) autoreactive antibodies (Abs), upon exposure to mercuric chloride (HgCl2). Laminin is an important autoantigenic target of the anti-GBM Abs, absorbing approximately 30% of the anti-GBM reactivity. Although many anti-GBM Abs have undergone isotype switching, it is currently unclear whether affinity maturation occurs during the HgCl2-induced autoimmune response. To address this question we analysed the rearranged immunoglobulin heavy chain variable-region genes (VHDJH regions) of 15 mAbs that were previously obtained from HgCl2-treated rats. Seven of these mAbs exhibit reactivity towards laminin. Our study showed that the VH-gene usage of antilaminin mAbs is largely restricted to the PC7183 VH-gene family (six out of seven). In addition, we demonstrated that at least three out of six laminin reactive and five out of six non-laminin-binding mAbs are encoded by germline VH genes (a total of eight out of 12 mAbs). Of the eight mAbs that are encoded by germline VH genes, seven are of a non-immunoglobulin M (IgM) isotype, indicating that isotype switching has occurred in these mAbs in the absence of somatic mutations. The mutations observed in the VH genes of the four remaining mAbs do not provide strong evidence for antigenic selection. The data support the notion that B cells in this model of MGP are not subjected to affinity maturation and probably result from polyclonal B-cell activation.

Amino Acid Sequence↗
PubMed2000

Most marginal zone B cells in rat express germline encoded Ig VH genes and are ligand selected.

The present study was performed to analyze whether marginal zone B (MZ-B) cells in nondeliberately immunized adult rats are selected on basis of the specificity of their B cell receptor, and to determine to what extent memory B cells contribute to the MZ-B cell subset. To this end, the Ig PC7183 V(H) gene repertoire was studied among V(H)DJ(H)-mu transcripts expressed in four sequential stages of B cell development, of two individual untreated adult rats. B cell subsets, i.e., pro/pre-B cells and newly formed B (NF-B) cells from bone marrow, and recirculating follicular B cells and MZ-B cells from spleen were sorted by flow cytometry. In addition, from one these rats, cells were microdissected from follicular and MZ areas of the spleen and productive PC7183 V(H) gene rearrangements were analyzed for the presence of somatic mutations. Sequence analysis reveals that most MZ-B cells in the adult rat, either defined by flow cytometry or by their anatomical location in the spleen, express germline encoded V(H) genes (naive MZ-B cells) and a minor fraction (about 20%) of the MZ-B cells carry somatic mutations (memory MZ-B cells). In addition, we show that naive MZ-B cells are a selected population of cells, both based on PC7183 V(H) gene repertoire and on the length of the Ig heavy (H) chain complementarity-determining region 3 (H-CDR3) region, i.e., PC7183 V(H)DJ(H)-mu transcripts of MZ-B cells carry significantly shorter H-CDR3 regions than other B cell subsets.

Amino Acid Sequence↗
PubMed1999

The origin of marginal zone B cells in the rat.

The marginal zone is a unique compartment that is only found in the spleen. Rat marginal zone B cells (MZ-B) can be distinguished from other B cells, e.g. recirculating follicular B cells (RF-B), by several phenotypic characteristics. Typically MZ-B cells are surface (s)IgMhi, sIgDlo and CD45R(B220)lo, whereas RF-B cells are sIgMlo, sIgDhi and CD45Rhi. In addition, MZ-B cells stain strongly with HIS57, a newly developed monoclonal antibody. The developmental pathway and origin of MZ-B cells are not exactly known. However, previous studies indicate that recirculating (i. e. thoracic duct) B cells can give rise to MZ-B cells. Here the origin of (naive) MZ-B cells was studied using adriamycin (doxorubicin)-induced B cell depletion. Using three-color flow cytometry and immunohistology we show that 2 days after a single i.v. injection of the anti-tumor drug adriamycin only RF-B cells can be detected, while all other B cell subpopulations are depleted, including all bone marrow precursor B cells. By studying the sequential reappearance of various B cell subsets and their precursors after adriamycin administration we show that MZ-B cells and the splenic marginal zone can be detected at a time point at which newly generated B cells (immature B cells) are not yet present. Given the observation that only RF-B cells were present at this time, we conclude that RF-B cells are the immediate MZ-B precursor cells.

Animals↗
PubMed1998

Presence of germline and full-length IgA RNA transcripts among peritoneal B-1 cells.

Next to conventional B cells (or B-2 cells), peritoneal B-1 cells have been shown to contribute significantly to the production of IgA-secreting plasma cells in the gut. Evidence for this was mainly based on studies comprising manipulated animals, including lethally X-irradiated and transgenic mice. To examine the ability of peritoneal B-1 cells from untreated mice to switch actively to IgA in vivo, we performed RT-PCR analysis on FACS-sorted peritoneal B-cell subsets from untreated BALB/c mice in order to examine the presence of germline C alpha mRNA and mature C alpha mRNA transcripts. Germline C alpha and mature C alpha transcripts were readily detectable in peritoneal B-1 cells (defined as IgMbright/IgDdull), but not, or very little, in peritoneal B-2 cells (defined as IgMdull/IgDbright). Moreover, by subdividing the B-1-cell population in CD5+ B-1a cells and CD5- B-1b cells, it was shown that in vivo expression of germline C alpha and mature C alpha transcripts was largely restricted to the B-1b-cell lineage. These results indicate that peritoneal B-1 cells indeed are capable to switch to IgA under normal physiological conditions and hereby further support the view that B-1 cells contribute significantly to the mucosal IgA response, albeit this function appears to be restricted to the B-1b-cell subset.

Animals↗
PubMed1997

Monoclonal gammopathies in aging mu, kappa-transgenic mice: involvement of the B-1 cell lineage.

Monoclonal gammopathies (MG) are monoclonal proliferative disorders of B cells at the differentiation stage of Ig production. They can be detected in the serum, either as transient or as persistent homogenous immunoglobulin (H-Ig) components. The exact phenotype, localization, and cell lineage origin of the precursor cells of MG are unknown, but may be crucial for both the correct diagnosis and for timely efficient treatment of the malignant forms. We used for the first time transgenic (Tg) mice (Sp6; mu/kappa) to study the origin of MG. In the mu, kappa Tg mice a small proportion of B cells can still produce endogenous IgM. These cells are of B-1 cell origin. The MG in Tg mice showed a later onset and a lower frequency than those in littermate control mice, mainly due to a four times lower frequency of benign monoclonal gammopathy. The 10% of B-1 cells that were able to produce endogenous Ig led to the development of MG in a frequency that was half the number of MG found in normal littermates. None of the MG in Tg mice produced an Ig of the Tg origin and therefore it can be concluded that they originated from B-1 cells.

Aging↗
PubMed1997

Expression of HIS50 Ag: a rat homologue of mouse heat-stable antigen and human CD24 on B lymphoid cells in the rat.

Recently, a cDNA encoding a newly identified rat antigen (HIS50 Ag) that binds to monoclonal antibody (mAb) HIS50 was cloned and shown to be homologous to cDNA encoding murine heat-stable antigen (HSA) and human CD24. Here we show that, like CD24 and HSA, at least part of HIS50 Ag is inserted into the plasma membrane by a glycosylphosphatidylinosito: (GPI)-lipid linkage and we describe its expression in rat haemolymphopoietic tissues. HIS50 Ag expression was almost exclusively confined to B lymphoid cells, the vast majority of T lymphoid cells, erythroid and myeloid cells were HIS50+. Cell suspension analysis indicated that in bone marrow (BM) almost all Thy-1+ cells, HIS24+ cells [HIS24 recognizes the B-cell form of leucocyte common antigen (LCA)], terminal deoxynucleotidyl transferase-positive (TdT+) cells and (c + s)kappa cells expressed HIS50 Ag, and all (c + s)mu 1 cells. A presumably early population of B lymphoid cells, expressing HIS24 Ag without HIS50 Ag, TdT or immunoglobulin HIS24+HIS50+ TdT Ig+), constituted 1.6% of BM nucleated cells. In blood, one-fifth of mononuclear cells were HIS50+, and about 85% of these expressed mu and/or kappa chains. In spleen, flow cytometry analysis and immunohistology demonstrated heterogeneous expression of HIS50 Ag: immunoglobulin M (IgM)bright cells (as found largely in red pulp and marginal zone) were HIS50bright, while IgMdull cells expressed low or undetectable levels of HIS50 Ag. Germinal centre B cells expressed high levels of HIS50 Ag. Germinal centres of lymph nodes and tonsil of man also bound HIS50. We conclude that HIS50 Ag expression in the haemolymphopoietic system of rat is virtually restricted to the B lineage.

Animals↗
PubMed1996

B-1 cells and their reactivity with the murine intestinal microflora.

IgA secreting cells located in the lamina propria of the gut are a prominent feature of the mucosal immune system, which serves to protect the body from the continuous threat to infection by intestinal bacteria. In this review we summarize briefly the evidence that these IgA secreting cells have a dual origin and are derived either from conventional B cells or from B-1 cells. Furthermore, we show both at polyclonal and monoclonal levels that the major antigenic target of B-1 cell derived IgA are normal intestinal bacteria. Coating of intestinal bacteria with IgA is thought to result in immune exclusion, as shown for pathogenic bacteria. However, the bacterial microflora of the gut is an extremely stable ecosystem, despite the fact that the majority of intestinal bacteria are coated with IgA. We speculate here that these apparent contradictory functions of the humoral immune system, i.e. removal of bacteria and maintaining the normal gut flora might be exerted by IgA antibodies produced by the two B-cell lineages. The fixed and biased repertoire of B-1 cells might play a role in maintaining the normal intestinal flora. When pathogenic bacteria penetrate into the gut, conventional B cells may be induced in the Peyer's patches to produce high affinity, narrowly tuned IgA antibodies, leading to immune exclusion.

Animals↗
PubMed1996

Monoclonal immunoglobulin A derived from peritoneal B cells is encoded by both germ line and somatically mutated VH genes and is reactive with commensal bacteria.

We transferred peritoneal cells from BALB/c mice into C.B17 scid/scid mice. Six to eight months after injection, only cells with the B1 phenotype were retained in the spleens and peritoneal cavities of these mice. The lamina propria of the intestine contained many peritoneal, donor-derived, immunoglobulin A (IgA)-producing cells. The mesenteric lymph nodes of these mice were found to be a major site of proliferation and generation of IgA plasmablasts. We established eight IgA-producing hybridomas from the mesenteric lymph nodes of such mice, and all the hybridomas reacted with different but partially overlapping fecal bacterial populations. Cloning and sequencing of the VH genes of these hybridomas showed that two hybridomas utilized germ line-encoded VH genes while the VH genes of the six hybridomas showed somatic mutations, some of which are indicative of an antigen-driven selection process.

Animals↗
PubMed1995

Role of environmental antigen in the development of IgG+ cells in the bursa of fabricius.

IgG+ cells were detected in the bursa of Fabricius after hatching by immunofluorescence staining of single cells and immunohistologic studies using mAb anti-Ig gamma-heavy chain. The frequency of IgG+ cells in the bursa increased rapidly immediately after hatching. In histologic studies, most of the IgG+ cells were found in the medullary areas of the bursal follicle. Isolation of the bursa from the gut by bursal duct ligation before hatching suppressed the development of IgG+ cells in the bursa after hatching. In addition, administration of Ags into the bursal lumen just before bursal duct ligation caused a significant increase of IgG+ cells in the bursa compared with the isolated bursa. However, parenteral administration of Ags had no effect on the frequency of IgG+ cells in the isolated and normal bursa. These results suggest that Ags in the bursa are a prerequisite for the development of IgG+ cells in the bursa. Although the majority of IgG+ bursal cells were IgM+ IgG+ double-positive cells, sorted Bu1+ bursal cells, which contained 99.9% of IgG+ cells but not plasma cells, synthesized de novo IgM but little or no IgG. Therefore, it is likely that surface IgG on the bursal cells is not produced locally, but is trapped by IgM+ bursal cells. We speculate that Ags derived from the bursal lumen form immune complexes within the bursa, which are subsequently trapped on the surface of IgM+ bursal cells mediated either by Fc-receptors, C3 receptors, or surface Ig.

Animals↗
PubMed1995

Identification and kinetics of two recently bone marrow-derived B cell populations in peripheral lymphoid tissues.

In rats, the glycoprotein Thy-1 is expressed on recently bone marrow (BM)-generated B cells but not on mature recirculating follicular (RF) B cells. Here we demonstrate that Thy-1+ B cells consist of two phenotypically distinct, but developmentally related, populations: a population of newly formed (NF) B cells (IgMbr-IgDdu) that give rise to the second, less immature, Thy-1+ population of so-called early recirculating follicular (ERF) B cells (Thy-1+IgMduIgDbr) cells. These cells ultimately develop to RF-B cells (Thy-1-IgMbrIgDdu). Kinetic studies reveal that in absolute numbers per day most cells die at the transition of NF-B cells in the BM and those in the periphery: less cells die at later stages of B cell differentiation. Given the notion that this cell loss is not random, we speculate that NF-B cells and ERF-B cells may represent crucial steps during peripheral B cell development and their selection. Identification of their unique phenotype makes it possible to evaluate their roles in development of the antibody repertoire.

Animals↗