Immaturity of the human splenic marginal zone in infancy. Possible contribution to the deficient infant immune response

The immune response to polysaccharide Ag as present in the capsule of certain virulent bacteria has been demonstrated to be related to a functionally intact spleen. This immune response is almost completely defective in infancy. Because of this the development of cellular compartments in the human spleen was studied immunohistologically in frozen and paraffin tissue sections of 32 infant spleens (less than 2 y of age) and 6 spleens from children. Six cases of sudden infant death syndrome and 7 cases of infection or sepsis which were included showed no significant differences compared to the other cases. Whereas all other cellular compartments have completed their maturation to an adult-type immunophenotype and morphology within the first 5 mo, the infant marginal zone B cells show essentially different features compared to the adult situation. The main characteristics of the infant marginal zone B cells are the absence of CD21-(C3d/EBV-R) expression and the high percentage of cells strongly coexpressing IgM and IgD. As the marginal zone is supposed to be the site of the initiation of the immune response to polysaccharide Ag, there is a remarkable coincidence between the first appearance of MZ B cells with adult features, and the time of acquisition of the ability to mount an immune response to polysaccharides, including encapsulated bacteria.     

HLA-A*02:07 is a protective allele for EBV negative and a susceptibility allele for EBV positive classical Hodgkin lymphoma in China

HLA-A2 protects from EBV+ classical Hodgkin lymphoma (cHL) in Western Europe, but it is unknown whether this protective effect also exists in the Chinese population. We investigated the association of HLA-A2 and specific common and well documented HLA-A2 subtypes with EBV stratified cHL patients (n = 161) from the northern part of China. Quantitative-PCR and sequence-based subtyping was performed to identify HLA-A2 positive samples and their subtypes. 67 (42%) of the cHL patients were EBV+. There were no significant differences in percentages of HLA-A2 positivity between cHL and controls (65% vs 66%) and between EBV+ and EBV− cHL patients (70% vs 61%). The frequency distribution of HLA-A2 subtypes was significantly different between EBV stratified cHL subgroups and controls. This difference was most striking for the HLA-A*02:07 type with a frequency of 38% in EBV+ cHL, 8% in EBV− cHL and 20% in controls. Significant differences were also observed for the HLA-A*02:07, HLA-A2 (non-02:07) and the A2-negative typings between EBV+ cHL vs controls (p = 0.028), EBV− cHL vs controls (p = 0.045) and EBV+ vs EBV− cHL cases (p = 2×10⁻⁵). In conclusion, HLA-A*02:07 is a predisposing allele for EBV+ cHL and a protective allele for EBV− cHL in the northern Chinese population.     

Pre-immunotherapy serum CA27.29 (MUC-1) mucin level and CD69+ lymphocytes correlate with effects of Theratope® sialyl-Tn-KLH cancer vaccine in active specific immunotherapy

Patients with metastatic breast, colorectal or ovarian cancers received active specific immunotherapy (ASI) with Theratope® sialyl-Tn-KLH (keyhole limpet hemocyanin) cancer vaccine emulsified in Detox? adjuvant. The median log₂ anti-STn IgG titer generated by ASI, estimated by enzyme-linked immunosorbent assay with solid-phase ovine submaxillary mucin, was 5.322 (range = 0?–?9.322). Following ASI, 51 patients who generated titers higher than the median value for anti-STn⁺ mucin IgG survived longer than 46 patients who generated lower titers below the median. 38 of the patients were phenotyped for CD69 prior to ASI. The patients with lower numbers of CD69⁺ peripheral blood lymphocytes prior to immunotherapy (pre-ASI) also had low serum CA27.29 cancer antigen (MUC-1) levels, and had longer times to disease progression and improved survival following ASI. Elevated pre-ASI serum CA27.29 tumor antigen levels were associated with higher numbers of CD69⁺ PBL, with decreased anti-STn antibody production and decreased survival following ASI. The data are compatible with the hypothesis that elevated serum MUC-1 mucin is specifically immunosuppressive.     

Increased vascular resistance in paralyzed legs after spinal cord injury is reversible by training.

The purpose of the present study was to determine the effect of a spinal cord injury (SCI) on resting vascular resistance in paralyzed legs in humans. To accomplish this goal, we measured blood pressure and resting flow above and below the lesion (by using venous occlusion plethysmography) in 11 patients with SCI and in 10 healthy controls (C). Relative vascular resistance was calculated as mean arterial pressure in millimeters of mercury divided by the arterial blood flow in milliliters per minute per 100 milliliters of tissue. Arterial blood flow in the sympathetically deprived and paralyzed legs of SCI was significantly lower than leg blood flow in C. Because mean arterial pressure showed no differences between both groups, leg vascular resistance in SCI was significantly higher than in C. Within the SCI group, arterial blood flow was significantly higher and vascular resistance significantly lower in the arms than in the legs. To distinguish between the effect of loss of central neural control vs. deconditioning, a group of nine SCI patients was trained for 6 wk and showed a 30% increase in leg blood flow with unchanged blood pressure levels, indicating a marked reduction in vascular resistance. In conclusion, vascular resistance is increased in the paralyzed legs of individuals with SCI and is reversible by training.     

Lymphocyte subpopulations in peripheral blood and bone marrow in patients with idiopathic myelofibrosis

In 8 patients with idiopathic myelofibrosis (IM) T and B cells were studied in view of the possibility that immunological dysfunctions are involved in initiating or contributing to the bone marrow fibrosis. In peripheral blood the absolute numbers of E-SRBC and OKT3+ lymphocytes were significantly reduced; in addition a significant decline was observed in the proportion and absolute numbers of OKT8+ cells, resulting in a reversed Leu-3a/OKT8 ratio. An impaired B cell function was observed in 4 of the 8 patients, characterized by a disturbed in vitro pokeweed mitogen stimulated immunoglobulin synthesis and low serum immunoglobulin levels. Immuno-histological studies of the bone marrow demonstrated a scarcity of T cells but normal numbers of B cells. However, no correlation was noted between the observed deviations of B and T cells and the degree of bone marrow fibrosis determined by means of bone marrow histology and serum procollagen-III levels. These data are not sufficient to support the hypothesis that immunological changes in IM are primarily involved in the process of bone marrow fibrosis.     

Muscle glycogen recovery after exercise during glucose and fructose intake monitored by 13C-NMR

Van Den Bergh, Adrianus J., Sibrand Houtman, ArendHeerschap, Nancy J. Rehrer, Hendrikus J. Van Den Boogert, BerendOeseburg, and Maria T. E. Hopman. Muscle glycogen recovery afterexercise during glucose and fructose intake monitored by¹³C-NMR. J. Appl.Physiol. 81(4): 1495-1500, 1996.The purpose of this study was to examine muscle glycogen recovery with glucose feeding(GF) compared with fructose feeding (FF) during the first 8 h afterpartial glycogen depletion by using¹³C-nuclear magneticresonance (NMR) on a clinical 1.5-T NMR system. After measurement of the glycogen concentration of the vastus lateralis (VL) muscle in seven male subjects, glycogen stores of the VLwere depleted by bicycle exercise. During 8 h after completion ofexercise, subjects were orally given either GF or FF while the glycogencontent of the VL was monitored by¹³C-NMR spectroscopy every secondhour. The muscular glycogen concentration was expressed as a percentageof the glycogen concentration measured before exercise. The glycogenrecovery rate during GF (4.2 ± 0.2%/h) was significantly higher(P < 0.05) compared withvalues during FF (2.2 ± 0.3%/h). This study shows that1) muscle glycogen levels areperceptible by ¹³C-NMRspectroscopy at 1.5 T and 2) theglycogen restoration rate is higher after GF compared with after FF.

     

Tissue distribution of the C3d/EBV-receptor: CD21 monoclonal antibodies reactive with a variety of epithelial cells,medullary thymocytes,and peripheral T-cells

Summary The CD21 antigen has been described to represent CR2, the receptor for the complement fragment C3d and also the receptor for the Epstein-Barr virus (EBV). Monoclonal antibodies B2, HB5, and B-ly4 belong to the CD21 cluster, recognizing different epitopes of the CD21-molecule. Immunohistology of lymphoid tissues employing these antibodies showed the known staining of B cells and dendritic reticulum cells. Surprisingly, B2, but not HB5 or B-ly4, stained a distinct spot in the cytoplasm of a major proportion of medullary thymocytes, in almost all peripheral blood lymphocytes, and in a substantial amount of cells in T-cell areas of peripheral lymphoid tissues. This distinct cytoplasmic B2 staining was confirmed by immuno-electronmicroscopy. A similar B2+ cytoplasmic dot was observed in B-lymphoblastic lymphomas. Staining of non-lymphoid tissues showed reactivity with all three CD21 mAb with epithelial cells of skin, lung, esophagus, jejunum, colon, pancreas, tonsil, adrenal cortex, renal tubuli, and parotid glands, and with hepatocytes and tongue muscle. In addition, endothelial cells of small vessels showed B2 staining. One possible explanation for our results is, that apart from the presence of B cells and follicular dendritic cells, a CD21-molecule may be expressed by other cell types. However, a maybe more likely explanation may be that the recognized epitopes are not exclusively associated with the C3d/EBV-receptor, but also with other structures. In particular should the possibility be recognized of cross-reactivity with CR2-related proteins, encoded by the large gene family, to which CR2 belongs.     

The diversity of the immunohistological staining pattern of Sternberg-Reed cells

Lymph node tissue of eight cases of Hodgkin's disease of all different subtypes was studied with an immunoperoxidase technique for the detection of immunoglobulin G (IgG), J chain, kappa and lambda light chains, and alpha-1-antitrypsin in different types of Sternberg-Reed cells. It was found that L&H type Sternberg-Reed cells of the nodular lymphocyte predominance type contained IgG, J chain, and one type of light chain per individual cell. It is concluded that these findings indicate that L&H type Sternberg-Reed cells produce IgG and, consequently, are B immunoblasts. Typical and lacunar type Sternberg-Reed cells of mixed cellularity and nodular sclerosis subtypes were found to contain IgG and both types of light chains per individual cell. J chain was absent from these cells are alpha-1-antitrypsin was found in some of them in a paranuclear pattern, comparable to that in histiocytes. It is concluded that these findings exclude the production of IgG by these types of Sternberg-Reed cells and it is suggested that these Sternberg-Reed cells may be related to histiocytes on the basis of the similarity in the staining pattern for alpha-1-antitrypsin.     

DNA measurements in thin sections of lymphomas

The DNA content of the nuclei of lymphomas and a reactive lymph node was studied by light absorption measurements in Feulgen-stained thin (2 microns) sections of lymph node biopsies, using the TAS image analysis system. For each nucleus, the integrated light absorbance at 548 nm wavelength was multiplied by the square root of the nuclear area to obtain a parameter for DNA independent from the nuclear size. In a hyperplastic reactive lymph node with follicular hyperplasia, the distribution of DNA X square root area was different in centrocytes and centroblasts, being compatible with a diploid centrocyte fraction and a mainly tetraploid centroblast fraction, in which hypertetraploid (octoploid?) nuclei were present. Similar measurements in three follicular centroblastic-centrocytic lymphomas gave similar results, with the centroblasts mainly tetraploid. The DNA distribution was studied in sections of lymphomas of high and low grades of malignancy, classified visually on the number of mitoses seen per field. The distribution width, from the smoothed histogram as the DNA X square root area values beyond the maximum peak frequency, appeared to be larger in the high-grade malignant lymphomas, in accordance with their higher number of mitoses.