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Immunologic markers of Burkitt's lymphoma cells.

Lymphocyte markers were studied on fresh cells from 30 patients with Burkitt (L3) leukaemia and cell lines derived from endemic and non-endemic Burkitt's lymphoma (BL) patients. We observed day-to-day variations of lymphocyte marker expression by cultured lines and, occasionally, differences between fresh and cultured cells. In L3 leukaemia, a wide range of phenotypes, including pre-B cell and mature monoclonal IgM + IgD positive B-cell phenotypes, was observed. Most often, the cells expressed high-density monoclonal surface IgM without IgD and lacked IgG Fc, complement and Epstein-Barr virus receptors. Blast cells from rare patients featured monoclonal IgG or IgA instead of IgM. Cases with light chains of the lambda type were more frequent than those with kappa chains. Monoclonal immunoglobulins were found in serum or urine from eight of 20 patients studied. These results are compared with data from the literature on endemic and non-endemic BL and discussed with respect to the maturation stage reached by the cells. In the study of both fresh and cultured cells, we demonstrated a correlation between variant chromosomal translocations and light-chain types, the cells from patients with a t(2;8) translocation expressing kappa and those with a t(8;22) expressing lambda chains, with one exception Vimentin expression was absent or weak in most BLs studied (lines or fresh cells) and in cells from patients with Langer-Giedion syndrome, in contrast to most other lymphomas and leukaemias and normal lymphoblastoid cell lines.

Burkitt Lymphoma↗

Histogenesis of Burkitt's lymphoma: a B-cell tumour of mucosa-associated lymphoid tissue.

The designation Burkitt's lymphoma (BL) has proved to be of great convenience but has left undetermined the histogenesis of the tumour and its relationship to other B-cell lymphomas. One definition proposed for BL has been based on its relationship to Epstein-Barr virus (EBV). The EBV negativity of some BLs and the association of EBV with other non-Hodgkin's lymphoma, however, makes this definition unsatisfactory. Cytogenetic changes involving the translocations of part of chromosome 8 also are not specific for BL. In the Kiel classification, BL appears as a lymphoblastic lymphoma. However, lymphoblastic lymphomas and leukaemias arise from pre-B and early T cells, whereas BL shows characteristics of a more mature B cell. Mann et al. (1976) considered BL to be related to follicle centre-cell lymphomas. The morphology and immunological phenotype of BL are consistent with this hypothesis, although it would appear that BL is more restricted in its capabilities of further differentiation than other follicle centre-cell lymphomas. This lack of differentiation may be related to EBV infection. The characteristic anatomical distribution of BL is quite unlike that of most follicle centre-cell lymphomas and should be considered in the search for its histogenesis. BL involves the jaws during the period of maximum dental development, and also the salivary glands, thyroid, abdominal viscera and abdominal lymph nodes. Massive involvement of the breasts during pregnancy and lactation is characteristic.(ABSTRACT TRUNCATED AT 250 WORDS)

Africa↗

[Significance of preclinical emergency treatment for the prognosis of patients with severe craniocerebral trauma].

In a prospective study in 147 unconscious patients (Glasgow-Coma-Scale less than or equal to 7) we examined the relevance of preclinical care for posttraumatic prognosis-basic life support (BLS) referring to ventilation/oxygenation and circulation, as well as advanced trauma-specific treatment (ATT) referring to medication and positioning. Procedures providing oxygenation and stable cardiovascular function are found to be most important. The overall survival rate amounts to 53.7 per cent (79 of 147 patients). Whereas 56.6 per cent (77 of 136 patients) of the patients being preclinically attended by a physician, survive, the survival rate is only 18.2 per cent (2 of 11 patients) among those not medically cared for. 31.9 per cent (47 of 147 patients) receive trauma-adequate optimal prehospital care, and an additional 29.2 per cent (43 of 147 patients) obtain an acceptable treatment, whereas the remaining 38.8 per cent (57 of 147 patients) must be considered insufficiently for care. Patients with optimal preclinical care have a statistically significant higher survival rate in comparison to the whole group of patients-70.2 per cent vs. 53.7 per cent-and to those receiving a less sufficient attention-70.2 per cent vs. 46.0 per cent. Besides the severity of the cerebral trauma, the quality of the preclinical medical attention, too, has been proven to be of great importance for post-traumatic course and outcome in patients with severe head injury.

Brain Injuries↗

A case of lymphoblastic lymphoma with aberrant morphologic feature.

We report a case of 33-year-old Japanese female who had B-cell lymphoblastic lymphoma with Burkitt's lymphoma (BL)-like morphologic feature. Both breasts were involved and the resected tissue showed starry sky macrophages and a proliferation of lymphoblasts containing lipid droplets. The nucleus of the lymphoblast was oval or indented. The neoplastic cells examined expressed TdT, CD10, CD14, CD38, and WH14 (a marker of pre-B cell leukemia/lymphomas). Southern blotting analysis showed a rearrangement of the immunoglobulin heavy chain gene and germline configurations of T-cell receptor gene and c-myc 3rd exon gene. The immunophenotype and genotype of this neoplasm were different from those of previously reported BLs, but identical to those of B-cell lymphoblastic lymphoma. This case, therefore, was regarded as B-cell type lymphoblastic lymphoma containing lipid droplets.

Adult↗

[Recent progress made in the classification of lymphoid and monocytoid leukemias and of lympho- and reticulo-sarcomas].

New methods helpful in the classification of lymphoid and monocytoid leukaemias and haematosarcomas have recently become available. Among the most valuable procedures have been those detecting immunological markers and the ultrastructural analysis permitted by convention and scanning electron microscopy. The results of these studies, taken together with a meticulous morphologic examination on Giemsa smears allow a more subtle classification on these neoplasias. Among the most interesting points, one can list: a) The description of macroglobulinemic proplasmocytic leukaemia; b) The observation that all the prognostic parameters in the four types of common acute lymphoid leukaemia (ALL) (prolymphocytic, microlymphocytic, macrolymphocytic, prolymphoblastic) such as age, tumour mass (or leucocytosis are related to the cytological type); T marker may be found in all these types, except for the prolymphoblastic one; c) T or B immunoblastic acute lymphoid leukaemias have been described as a fifth type of ALL; d) The lymphosarcomas which can be histologically nodular (composed of B cells) or diffuse (composed of cells presenting B, T or no markers) can be cytologically prolymphocytic or lymphoblastic (or lymphoblastoid) if they are nodular, prolymphocytic, lymphoblastic, or immunoblastic if they are diffuse; true (African) Burkitt's lymphosarcomas (BLS) must be distinguished from all the pseudo (non-African) Burkitt's lymphosarcomas which have been described elsewhere and which are either immunoblastic or lymphoblastic (oid) lymphosarcomas with a few macrophages; e) The diagnosis of reticulosarcoma which was in the past abusively carried out (because of confusion with immunoblastic lymphosarcoma) is based on the presence of many reticluins fibers at histological examination and on the cytological aspect of the cells on smears (the distinction of those cells with immunoblasts is easy).

B-Lymphocytes↗

A mutant p21 cyclin-dependent kinase inhibitor isolated from a Burkitt's lymphoma.

The growth arrest mediated by p53 is caused at least in part by the p53 mediated expression of p21 (p21waf1/Cip1). Since only one-third of primary Burkitt's lymphomas (BL) demonstrate mutations in the p53 gene, we examined the structural integrity of the p21 coding region by single-strand conformational polymorphism and DNA sequence analysis to determine the extent to which this gene is mutated in BL. Of 34 BLs analyzed, a frequent change (38%) at codon 31 that replaced Ser with Arg was found in 13 samples, 10 of which were from Africa. This change at codon 31 is also detected in peripheral blood DNA from normal subjects and may thus represent a polymorphism. One BL cell line, DH978, carried a change at codon 63: Phe to Leu. This mutation was heterozygous, and both the wild-type and the mutated p21 mRNA were expressed in the tumor cell line. By transfection experiments, the mutant p21 was less efficient in suppressing clonogenicity than wild-type p21. To our knowledge, this is the only mutation described in p21. The availability of this mutant p21 should further help in functional studies of p21.

Base Sequence↗

Progress in the classification of lymphoid and/or monocytoid leukemias and of lympho and reticulosarcomas (non-Hodgkin's lymphomas).

New methods helpful in the classification of lymphoid and monocytoid leukaemias and haematosarcomas have recently become available. Among the most valuable procedures have been those detecting immunological markers and the ultrastructural analysis permitted by convention and scanning electron microscopy. The results of these studies, taken together with a meticulous morphologic examination on Giemsa smears allow a more subtle classification on these neoplasias. Among the most interesting points, one can list: a) The observation that all the prognostic parameters in the four types of common acute lymphoid leukaemia (ALL) (prolymphocytic, microlymphoblastic, macrolymphoblastic, prolymphoblastic) such as age, tumour mass (or leucocytosis) are related to the cytological type; T marker may be found in all these types, except in the prolymphoblastic; b) T or B acute lymphoid immunoblastic leukaemias has been described as a fifth type of ALL; c) The lymphosarcomas which can be histologically nodular (composed of B cells) or diffuse (composed of cells presenting B, T or no markers) can be cytologically prolymphocytic or lymphoblastic (or lymphoblastoid) if they are nodular, prolymphocytic, lymphoblastic or immunoblastic if they are diffuse; true (African) Burkitt's lymphosarcomas (BLS) must be distinguished from all the pseudo (non-African) Burkitt's lymphosarcomas which have been described elsewhere and which are either immunoblastic or lymphoblastic (oid) lymphosarcomas with a few macrophages. d) The diagnosis of reticulosarcoma which was in the past abusively carried out (because of confusion with immunoblastic lymphosarcoma) is based on the presence of many reticulins fibers at histological examination and on the cytological aspect of the cells on smears (the distinction of those cells with immunoblasts is easy).

Azure Stains↗

Type II pneumocytes revisited: intracellular membranous systems, surface characteristics, and lamellar body secretion.

BACKGROUND: Type II pneumocytes, the producers of pulmonary surfactant, have been extensively studied during the last 20 years because of the importance of their metabolism in lung function and integrity. The ultrastructural studies of the 1970s and 1980s have shown that these cells present unique elements. EXPERIMENTAL DESIGN: In this work, we used thin-section, freeze-fracture, and fracture-flip electron microscopy techniques to obtain new information on the ultrastructural peculiarities of isolated rat type II pneumocytes, focusing our study on the intracellular membranous systems and their interrelationships and the microanatomy of their plasma membrane during secretory process. RESULTS: In thin-sections of pneumocytes postfixed with osmium tetroxide and potassium ferricyanide, we observed that lamellar bodies (LBs) are usually connected to membranes of the endoplasmic reticulum, and seem to emerge and grow from them. Unusual connections between the endoplasmic reticulum and mitochondria were detected, as well as numerous "bar-like structures" (BLSs), most of them in the early stages of development and often generating from the nuclear membrane. Membranes of the smooth endoplasmic reticulum that closely follow the outlines of mitochondria also appear to be the origin of some BLSs. Possible transition forms, BLS--LB, were also detected, although they were rare. New images of the surface of the pneumocytes and its changes during LB secretion showed a segregation and clearing of membrane particles at the areas of LB extrusion. CONCLUSIONS: We propose that LBs can originate directly from membranes of the endoplasmic reticulum or from BLSs. An indirect participation of mitochondria appears possible. The plasma membrane of pneumocytes displays structural changes associated with the secretion of LBs as visualized by a redistribution of intramembrane and surface particles.

Animals↗

Cyclins D1 and D2 are differentially expressed in human B-lymphoid cell lines.

The cyclin D1 gene can be transcriptionally activated in lymphoid tumours as a result of chromosomal rearrangements but is normally silent in B and T lymphocytes. By isolating cyclin D1-related cDNAs from a B-lymphoid cell line, we identified clones that contain the coding sequences of human cyclin D2. The predicted 289 amino acid protein shares 63% identity with human cyclin D1. Although cyclin D2 transcripts were detected in many lymphoid cell lines, it was not ubiquitously expressed and there was no apparent correlation with cyclin D1 levels. For example, two B-cell leukaemia lines, JVM-2 and Karpas 620, both of which have 11q13 translocations and express cyclin D1, contained markedly different amounts of cyclin D2. An obvious distinction between these cells is that the JVM-2 line, which expresses high levels of cyclin D2, was immortalized by Epstein-Barr virus (EBV). We subsequently found that cyclin D2 is consistently expressed in group III Burkitt's lymphoma (BL) and in lymphoblastoid cell lines immortalized by EBV, but not in group I BLs, in which expression of the EBV genome is more restricted. The data imply that the D-type cyclins may have non-overlapping functions at specific stages of lymphocyte differentiation and that the expression of cyclin D2 may be influenced, directly or indirectly, by EBV.

Amino Acid Sequence↗

Work-related injuries and illnesses associated with child labor--United States, 1993.

During 1993, an estimated 2.1 million persons aged 16-17 years in the United States were employed. Although many children aged <16 years work, employment data are neither routinely collected nor reported for this age group, and there are no reliable estimates of the number of children in this age group who work. During summer months, when most children are not in school, employment and hours worked by children aged <18 years increase substantially. To characterize workplace-related health and safety hazards for children, CDC's National Institute for Occupational Safety and Health (NIOSH) analyzed 1993 data for workers aged <18 years from the Survey of Occupational Injuries and Illnesses (SOII), a survey administered by the Bureau of Labor Statistics (BLS), U.S. Department of Labor. This report summarizes the results of this analysis and indicates that substantial numbers of persons aged <18 years sustain work-related injuries and illnesses each year.

Absenteeism↗

Variation in the sequence of Epstein Barr virus nuclear antigen 1 in normal peripheral blood lymphocytes and in Burkitt's lymphomas.

We have examined sequence variations in the EBNA-1 protein of EBV in normal peripheral blood lymphocytes (PBL) and Burkitt's lymphomas (BL). We find two EBNA-1 strains P (prototype) and V (variant) which differ by 15 amino acids. Each strain has two subtypes defined by the amino acid at position 487 (P-ala, P-thr, V-pro and V-leu). In PBLs from 32 normal individuals, up to three of these subtypes were found in each sample, but the V strain did not occur in the absence of P strain viruses, nor was the V-leu subtype ever observed in normal PBL. In BLs only a single subtype was observed in each tumor. The P-thr and V-leu subtypes were more frequently seen than the P-ala and V-pro subtypes, which occurred in only two and one of the 36 tumor samples respectively. The P-thr was the most commonly observed subtype in peripheral blood of both American and African lymphocytes as well as in African tumors. However, in 11 of 12 American tumors, the EBNA-1 subtype was V-leu. These data indicate that some EBNA-1 subtypes are more likely to lead to oncogenesis, and one subtype, V-leu, appears only to occur in tumors.

Amino Acid Sequence↗

[Treatment strategies in mechanical and electrical cardiovascular failure].

Guidelines in cardiopulmonary resuscitation [CPR] improve survival of patients in cardiac arrest. Programs with both Basic Life Support [BLS], promptly initiated, and early defibrillation must be designed to motivate persons trained in prehospital CPR. The most frequent lethal rhythm in cardiac arrest is ventricular fibrillation [VF], affecting over 75% of patients. Early defibrillation must have the highest priority as the only method for termination of VF and being the major determinant for survival. Administration of 1.0 mg epinephrine iv as the drug of choice, followed by defibrillation [360 J] in patients with recurrent/persistent VF remains gold standard in Advanced Cardiac Life Support [ACLS]; epinephrine administered in the same, or higher, dosage can be repeated every 3-5 minutes followed by defibrillation within 30-60 seconds. Management of asystole and pulseless electrical activity is discussed, including the necessity to search for treatable causes as one major action, in addition to performing ACLS and administering epinephrine.

Adrenergic Agonists↗

[Resuscitation].

By the measures of basic life support (BLS) as well as those of advanced cardiac life support (ACLS) a large portion of the 8,000 to 10,000 victims of sudden circulatory arrest in Switzerland might be resuscitated successfully without permanent neurological deficits. Prerequisites are an early installation of measures as well as the control of the rationale and the individual techniques by trained personnel. The single most important measure is electric defibrillation of ventricular fibrillation. With the aid of automatic defibrillators it can be made available to a wider range of users. Pharmacotherapy is of minor importance.

Algorithms↗

Measurement of radiofrequency electromagnetic fields in and around ambulances.

Electromagnetic interference (EMI) with medical devices can threaten patient safety. More information is needed regarding circumstances in health care environments in which electromagnetic (EM) field strengths are expected to be high, such as emergency/transport. In ambulances medical devices and communications equipment must function properly in close proximity. This study characterized EM fields in and around ambulances under realistic conditions. Two types of ambulances were surveyed: the advanced life support (ALS) unit and the basic life support (BLS) unit. The surveys were conducted on-site using the ambulance mobile radio as the primary source of EM energy. Broadband field-strength measurements were collected at various locations in and around the ambulance to map interior and exterior EM field distributions. Nine ambulances were surveyed. In addition to the transmitter power and frequency, the field strengths measured were shown to be dependent upon the shielding provided by the ambulance roof and proximity of the measurement probe to the antenna. Field-strength measurements frequently exceeded the 3 V/m standard immunity level for devices set by the IEC Standard 601-1-2. The results indicate that the ambulance environment presents a considerable challenge to medical devices specifically used for emergency medical care. In order to assure their proper operation, medical devices used for transport emergency care must be able to withstand exposure to EM field strengths comparable to those reported in this study.

Ambulances↗

Differential expression of nucleoskeleton- and cytoskeleton-associated proteins in Burkitt lymphoma-derived and Epstein-Barr virus-immortalized lymphoblastoid cell lines.

Mouse monoclonal antibodies raised against nuclear bodies isolated from an EBV-immortalized lymphoblastoid cell line (LCL) known to contain several viral and cellular proteins (Jiang et al., Exp. Cell Res., 197: 314-318, 1991; Szekely et al., J. Gen. Virol., 76: 2423-2432, 1995; Szekely et al., J. Virol., 70: 2562-2568, 1996). Seventy six clones gave detectable immunofluorescence staining on LCLs. Five independent monoclonal antibodies detected a group of apparently novel, high M(r) (> 200,000) proteins that shared common features of subcellular distribution. In LCLs, these proteins were preferentially associated with vimentin filaments in the cytoplasm and with distinct nuclear foci. The appearance of the latter differed from the premyelocytic leukemia-associated protein, EBV nuclear antigen #5, and retinoblastoma-protein-positive bodies that were used for immunization. They seemed to be connected to the cytoplasmic filaments through thin fibrillar nuclear structures. In mitotic cells, these complex structures rearranged into a perichromosomal basket that was associated with vimentin filaments. The target proteins, operationally designated as proteins associated with nuclear dots and cytoplasmic filaments (pNDCFs), were not present in resting human B cells or were expressed at a low level. The level increased considerably after EBV infection or mitogenic stimulation by interleukin 4 and anti-CD40 antibodies. In Burkitt lymphoma (BL) type I lines phenotypically representative of the in vivo tumors, the pNDCFs were either absent or exclusively localized to the nucleus, usually to well-defined nuclear foci. EBV-positive type I BLs often shift to a more LCL-like (type III) phenotype during prolonged in vitro propagation. Type I cells express only EBV nuclear antigen 1 and the surface markers CD10 and CD77, whereas type III express all nine growth-associated EBV-encoded proteins and a gamut of B-cell activation markers. Most of the type III BL cell lines contained increased amounts of pNDCFs bound to cytoplasmic filaments, as seen in the LCLs. We propose that the expression of vimentin-associated pNDCFs should be included in the definition of type III BL phenotype.

Burkitt Lymphoma↗

Impact of emergency medical helicopter service on mortality for trauma in north-east Italy. A regional prospective audit.

The hypothesis that high level on-the-field ATLS could influence mortality in severe trauma patients was tested by means of a prospective study. During a 7 month period, data of all the victims of severe involuntary trauma (road traffic accidents, work and sport accidents) in 3 Provinces of north-east Italy were entered in a database and analysed. The whole area is covered by a single emergency service which has direct control over all the ambulances and the Emergency Helicopter Service (EMHS). The area concerned by the study has a surface of 7,300 kmq with a population of 1 million inhabitants and is served by 12 first level hospitals and 4 second level institutions (trauma centres). All the patients who were still alive at the time of arrival of the first rescuers were considered, but only severe trauma patients with ISS > 15 were enclosed into the study. All the patients were followed up to their discharge from the ICUs (end point). There were three different rescue approaches: 82 Patients (GROUP A) were rescued by EMTs with BLS training, transported to the nearest level 1 hospital for stabilisation and subsequently transferred to a trauma center; 98 Patients (GROUP B) were rescued by EMTs and directly transported to a trauma centre which was the nearest institution; 42 Patients were rescued on the scene by the EMHS team including an anaesthesiologist with 10 years experience in trauma care and directly transported to a trauma centre after full on-the-field stabilisation (GROUP C) RESULTS: 222 severe trauma patients (ISS > 15) were considered. Mean ISS was 35.1 +/- 18.2 in group A, 33.4 +/- 19.6 in group B and 36.0 +/- 17.8 in group C. 67 patients died previous to ICU discharge (31%). 31 over the 82 pts in Group A (38%) died. 23 of them died even before reaching the trauma centre. The mean time elapsed between the first emergency call and the arrival at the trauma centre was 162 min (90'-300'). Mean ICU stay for patients who survived was 15 days. In Group B 31 over 98 patients (32%) died before ICU discharge. The mean time between the emergency call and hospital admission was 27'. Mean ICU stay for patients who were discharged, was 13 days. 5 over 42 patients rescued by the EMHS (Group C) died, none of them in the pre-hospital setting. Stabilisation included tracheal intubation in 34 cases (81%) and thoracic drainage in 6 (14%). All the patients arrived at the hospital with 2 i.v. line. The average amount of infused fluids were 600 mls of colloids and 810 mls of crystalloid. 13 patients with hypotension received and average of 1000 mls of colloids and 1200 mls of crystalloid. The average time elapsed between the emergency call and the final admission to the definitive care institution was 55'. Mean ICU stay was 11 days. Mortality rate in this group was 12%, significantly lower than in group A (p < 0.005) and group B (p < 0.05).

Air Ambulances↗

Emergency medical service providers' role in the early heart attack care program: prevention and stratification strategies.

Emergency Medical Services-Early Heart Attack Care (EMS-EHAC) is a community-based program where paramedics increase the consumer's awareness about early chest pain symptom recognition. EMS-EHAC prevention, along with seamless chest pain care (between the paramedic and chest pain emergency department) can be the basis for an outcome-based study to examine the impact of advanced life support EMS. Studies that show the impact of care given by paramedics on the outcome of patient care must be designed to demonstrate the value and the cost benefit of providing advanced life support (ALS). Third party payers are going to examine if there are significant quality differences between ALS and basic life support (BLS) services. If significant benefits of ALS care cannot be demonstrated, the cost differences could potentially place the future of advanced life support paramedic programs in jeopardy. A positive outcome resulting in a lower acute cardiac event, and the realization of the cost benefits from the EMS-EHAC program could be utilized by EMS management to justify or expand advanced life support programs.

Allied Health Personnel↗

Phenotype-dependent differences in proteasome subunit composition and cleavage specificity in B cell lines.

We have compared the subunit composition and enzymatic activity of purified 26S proteasomes from Burkitt's lymphoma (BL) cells and in vitro EBV-transformed lymphoblastoid cell lines (LCLs) of normal B cell origin. Low expression of the IFN-gamma-regulated beta low molecular mass polypeptide (Lmp)2, Lmp7, and MECL-1 was demonstrated in a panel of seven BL lines that express the germinal center cell phenotype of the original tumor. Coexpression of Lmp2 and Lmp7 with the constitutively expressed subunits delta and MB1 was demonstrated in the BL lines by immunoprecipitation and two-dimensional gel fractionation of the 20S proteasomes. Coexpression of these subunits correlated with reduced levels of chymotrypsin- and trypsin-like activities detected by the cleavage of fluorogenic substrates. Down-regulation of Lmp2 and Lmp7 and decreased chymotrypsin- and trypsin-like activities were also observed in purified proteasomes from a c-myc-transfected subline of the ER/EB2-5 LCL that has adopted a BL-like phenotype. A synthetic peptide analogue of the immunodominant epitope from the EBV nuclear Ag 4 (E4416-424Y) was cleaved by proteasomes from BLs and A1, while proteasomes from LCLs were inactive. Cleavage of the E4416-424Y peptide was not affected by treatment of the BL cells with IFN-gamma despite both significant up-regulation of Lmp2 and Lmp7 and reconstitution of chymotrypsin and trypsin-like activities against fluorogenic substrates to LCL-like levels. The results demonstrate that B cell lines representing different stages of B cell activation and differentiation express proteasomes with different subunit compositions and enzymatic activity. This may result in the generation of a distinct set of endogenous peptides and influence the immunogenicity of these cells.

B-Lymphocyte Subsets↗