Biomedical subjects

Shigeki Nabeshima

Publications and source records attributed to Shigeki Nabeshima.

At least 19 recordsLinked to original sources

PubMed2006

A comparison of the antitumor effects of interferon-alpha and beta on human hepatocellular carcinoma cell lines.

The antiviral, antiproliferative and immunomodulatory effects of type I interferons (IFNs) are well documented, however, few studies have been published concerning differences in the antitumor effects of IFN-alpha and beta. In the present study, differences in antitumor effect, including the antiproliferative effect, cell cycle change, apoptosis, and the IFN-stimulated gene (ISG) were examined by flow cytometry between IFN-alpha and beta on three human hepatocellular carcinoma (HCC) cell lines (HepG2, Huh7 and JHH4). The antiproliferative effect of both IFNs on the HCC cell lines was time- and dose-dependent, and IFN-beta was significantly stronger than IFN-alpha. The cell cycle effect by both IFNs was an S-phase accumulation, with IFN-beta having a tendency to increase the S-phase ratio more strongly than IFN-alpha, especially in Huh7. Apoptosis marker expression, Fas antigen and intracellular active caspase-3, was increased after the addition of IFNs, especially of IFN-beta. The expression of human leukocyte antigen-class I molecules, ISG-encoded protein, was increased after the addition of IFNs, especially of IFN-beta. These data suggest that IFN-beta has a greater antitumor effect than IFN-alpha on HCC of a very early stage in patients with chronic hepatitis C.

Antineoplastic Agents↗

PubMed2006

[Varicella-zoster virus symptoms and polyneuropathy in a patient with human immunodeficiency virus infection not improved until highly active anti-retroviral therapy added to acyclovir therapy].

In March 2003, a 34-year-old man with left facial palsy, dysphagia, and hoarseness treated with acyclovir suffered worsened dermatological and neurological problems. A routine blood test in early April showed the patient to be HIV-antibody positive, so he was transferred to our hospital. Blood analysis showed serum HIV-RNA at 96,000 copies/mL and a CD 4 count of 170/microL. Brain MRI taken on admission showed a T 2 high lesion in their left medulla. Acyclovir was thought to be ineffective due to reduced cell-mediated immunity because of the HIV infection, and HAART therapy was begun. After two months of HAART, skin lesions and the T 2 high lesion in left medulla improred. HIV-RNA became undetectable and the CD 4 count exceeded 500/microL. Intracellular cytokine analysis by flow cytometry showed a shift from Th 2 to Th 1 dominance. The elimination of VZV may thus have been promoted by the combination of acyclovir and HAART.

Acyclovir↗

PubMed2005

Interferon-alpha/beta upregulate IL-15 expression in vitro and in vivo: analysis in human hepatocellular carcinoma cell lines and in chronic hepatitis C patients during interferon-alpha/beta treatment.

Type I interferon (IFN) possesses antiviral and antitumor activities and also having an immune regulatory effect, activating cellular immune response and upregulating several cytokines. Recent study has shown that type I IFN upregurates the dendritic cell production of IL-15 capable of activating natural killer cells and CD8+ memory T lymphocytes. However, it is still unknown if type I IFN induces IL-15 production in non-immune cells and if type I IFN affects IL-15 production in vivo. The present study investigated the effect of type I IFNs on IL-15 expression in hepatocellular carcinoma (HCC) cell lines in vitro and in patients with chronic hepatitis C in vivo. When three HCC cell lines, Huh7, HepG2, and JHH4 were cultured in vitro, IFN upregulation of IL-15 expression was observed at both the mRNA and protein levels. In experiments using Huh7 cells, upregulation of IL-15 expression occurred within 24 h of the start of IFN stimulation, and both IFN-alpha and -beta dose-dependently increased IL-15 production in the range from 100 U/ml to 10,000 U/ml of concentration. IFN-beta showed stronger activity in IL-15 production induction in vitro than IFN-alpha. For in vivo examination, sera were obtained from 21 chronic hepatitis C patients treated with IFN and 29 healthy individuals, and the serum IL-15 level was quantified by ELISA. The serum IL-15 level of chronic hepatitis C patients before IFN treatment was similar to that of the healthy controls and significantly increased only during the IFN administration period. These results confirm that IFN-alpha/beta induce IL-15 production and also suggest that IL-15 may be associated with type I IFN-induced immune response.

Adult↗

PubMed2005

CD27(+) (memory) B cell decrease and apoptosis-resistant CD27(-) (naive) B cell increase in aged humans: implications for age-related peripheral B cell developmental disturbances.

To investigate age-related alterations in human humoral immunity, we analyzed the quantity and quality of peripheral B cell subsets, CD27-negative (CD27(-)) and CD27-positive (CD27(+)) B cells, by flow cytometry analysis in 54 aged individuals (mean age +/- SE, 74.6 +/- 0.7 years) and 30 young individuals (mean age +/- SE, 26.1 +/- 0.5 years). CD27(-) and CD27(+) B cells are regarded as naive and memory B cells, respectively. CD38, Ki-67, CD95 and bcl-2 were used as activation, proliferation and apoptotic markers. Susceptibility to apoptosis was evaluated by cell size and annexin-V binding in culture cells. The percentage of CD27(+) B cells was significantly lower in aged (mean, 19.2%) individuals than that in young individuals (mean, 28.2%). The opposite was true for CD27(-) B cells (mean, 80.8% in aged and 71.8% in young) (P < 0.01). The absolute number of CD27(+) B cells in aged individuals was significantly less than the number of CD27(-) B cells. The CD27(+) B cells from aged individuals showed little susceptibility to apoptosis, although CD95 expression on the CD27(+) B cells was significantly higher in the aged individuals than in the young individuals (P < 0.05). The CD38 and bcl-2 expression on the CD27(-) B cells was significantly higher in the aged individuals than in the young individuals (P < 0.05). In addition, the CD27(-) B cells from the aged individuals showed a decreased susceptibility to apoptosis compared with that of the young individuals. These findings suggested that human aging leads to both quantitative and qualitative alterations in the peripheral B cell developmental system, including memory and naive B cell balance and their surface phenotypes.

ADP-ribosyl Cyclase↗

PubMed2005

Kinetic analysis of Mycobacterium tuberculosis-specific cytokine production by PBMC in adults after BCG vaccination.

Although bacille Calmette-Guerin (BCG) has been used worldwide as the only vaccine for tuberculosis, its protective efficacy in human adults is controversial. To investigate human immunological responses to Mycobacterium tuberculosis after BCG vaccination, we analyzed IFN-gamma and IL-10 production by peripheral blood mononuclear cells (PBMC) from health-care workers five times throughout the year after BCG vaccination. Of 449 health-care workers, 36 (8.0%) were negative by the tuberculin skin test, and of these, 20 were vaccinated with BCG. Because all the subjects had received BCG vaccination as infants, the present vaccination was considered to be a revaccination. The cytokine responses of the vaccinated and control tuberculin skin-test-positive subjects (n = 6) were followed at 0, 2, 4, and 8 weeks and at 12 months. The mean IFN-gamma production by PBMC when cultured with purified protein derivative (PPD) gradually increased, reached a peak at week 8, and then declined until 12 months, with four exceptions who showed no IFN-gamma elevation. The IFN-gamma level of the vaccinated group at week 0 was significantly lower than that of the controls. The mean IL-10 production in response to PPD reached a peak at week 2, and then declined to its lowest point at week 8. These results indicate that the BCG vaccine can induce a type I cytokine response to M. tuberculosis in most tuberculin skin-test-negative adults at week 8, suggesting the immunological efficacy of vaccination.

Adolescent↗

PubMed2005

Serum antibody response to tuberculosis-associated glycolipid antigen after BCG vaccination in adults.

Tuberculous glycolipid antigens (TBGLs) are derived from the cell walls of Mycobacterium tuberculosis. Detection of anti-TBGL antibody in serum has recently become possible for the serodiagnosis of active tuberculosis. TBGL is not indigenous to M. tuberculosis, but it is widely found in Mycobacterium species. To elucidate the influence of M. bovis bacille Calinette-Guérin (BCG) vaccination, we assayed serum anti-TBGL antibody after BCG vaccination in adults. BCG vaccination was done for 20 Japanese healthcare workers with a negative tuberculin skin test reaction, and serum was collected 0, 2, 4, and 8 weeks and 1 year after vaccination. The tuberculin skin test became positive in 85% of the subjects. The mean anti-TBGL antibody titer remained negative throughout the observation period, but was elevated significantly compared with the pre-vaccination level, peaking at week 4 and showing a reduced level 1 year post-vaccination. These results showed that serological diagnosis using anti-TBGL antibody was not influenced by prior BCG vaccination.

Adult↗

PubMed2005

Helper T cell cytokine response to ribavirin priming before combined treatment with interferon alpha and ribavirin for patients with chronic hepatitis C.

The viral genotype and serum viral level influence the response to interferon (IFN) treatment in patients with chronic hepatitis C virus (HCV) viremia. The aim of this study was to investigate a possible relationship between early virological response and helper T (Th) cell cytokine expansion by 4 weeks of ribavirin (RIB) alone followed by IFN and RIB combined in patients with genotype 1b and a high HCV RNA level, patients reported not to respond well to IFN treatment. Eighty-one patients with genotype 1b and a high HCV RNA level, over 100 international unit per milliliter (KIU/mL) (by Amplicor HCV Monitor), were assigned to two groups: Group A (N = 40) with a 4-week RIB administration followed by a 24-week combination treatment, and Group B (N = 41) with a 24-week combination treatment only. Blood was obtained from each patient on the following schedule: at Baseline (4 weeks before day 0), on day 0 (initiation day of the RIB and IFN combination treatment), weeks 4 (4 weeks after the start of the combination treatment), and at the end of the combination treatment. Flow cytometry was used to investigate sequential changes of IFN-gamma producing (Th1) and interleukin-4 producing (Th2) cells from whole blood samples after stimulation with PMA and ionomycin. Serum HCV RNA clearances were 32.5% at week 4, 43.2% at week 8, 85.7% at the end of the combination treatment, and 22.9% within the 24-week follow-up in Group A; and 17.1%, 27.0%, 66.7% and 19.4% in Group B, respectively. The mean Th1/Th2 ratio significantly increased from 15.9 at baseline to 17.6 at day 0 with a decrease of Th2 cells, and then significantly decreased from 17.6 at day 0 to 15.5 at week 4 in Group A, while there was no significant change in Group B between baseline and day 0. In Group A, 13 patients with HCV RNA clearance within 4 weeks had a significantly increased Th1/Th2 ratio, from 14.0 at baseline to 22.1 at day 0, and then a significantly decreased ratio, from 22.1 at day 0 to 15.0 at week 4, while the others had no significant change in the ratio. RIB administration preceding combined treatment of RIB with IFN was more effective in Th2 cell expansion than the usual combined treatment of IFN with RIB and led to a relatively early virological clearance in chronic hepatitis C patients with genotype 1b and a high HCV RNA level.

Adult↗

PubMed2005

Amelioration of extrapontine myelinolysis and reversible parkinsonism in a patient with asymptomatic hypopituitarism.

A 37-year-old woman with a history of transphenoidal surgery and gamma knife treatment for prolactinoma was admitted because of pneumoniae with hyponatremia (Na 109 mmol/l). After the careful correction of the serum sodium level within 15 mmol/l/day, the patient developed parkinsonism. MRI of the brain disclosed a signal increase in the bilateral basal ganglias on T2-weighted images, a finding consistent with extrapontine myelinolysis (EPM). Interestingly, the parkinsonism fully disappeared after the replacement therapy of hydrocortisone for adrenal insufficiency due to hypopituitarism, and MRI 5 months later showed complete disappearance of the lesions, indicating the patient had ameliorated from the EPM.

Adult↗

PubMed2004

Downregulation of CXCR5 in CD27- B cells of HIV-1 infected patients.

The CD27(-) (naive) B cells of HIV-1 infected patients have been shown to be increased in frequency and to be activated, as indicated by high CD38 expression on the cell surface. CXCR5, a B cell chemokine receptor, is expressed on circulating CD27(-) (naive) B cells and plays a pivotal role in peripheral B cell development. To investigate the effect of HIV-1 infection on the expression of this chemokine receptor on naive B cells, the expression level of CXCR5 on CD27(-) B cells was examined in 19 drug-naive HIV-1 infected patients, 27 HAART-treated patients, and 20 controls. CXCR5 expression on CD27(-) B cells was significantly lower in drug-naive patients than in HAART-treated patients and controls (P < 0.01). CD27(-) B cells with high CD38 expression exhibited low CXCR5 expression. The CXCR5 expression level on CD27(-) B cells recovered to within the normal range after effective antiretroviral therapy. These findings suggested that HIV-1 infection induces a remarkable phenotypic alteration of naive B cells and that the activated naive B cells found in HIV-1 infection downregulate CXCR5 on their surface. Impaired homing of naive B cells may contribute to HIV-1 induced immunological deficiencies.

ADP-ribosyl Cyclase↗

PubMed2004

Maturation of monocyte-derived dendritic cells by Hochu-ekki-to, a traditional Japanese herbal medicine.

To investigate the immunological effect of the traditional Japanese herbal medicine (kampo), Hochu-ekki-to (HOT), on dendritic cells (DC), we examined in vitro if HOT would stimulate the maturation process of human monocyte-derived DC as do TNF-alpha and LPS. Monocytes from a healthy volunteer were cultured in the presence of IL-4 and GM-CSF, and the generated immature DC were stimulated with HOT, TNF-alpha, or LPS (HOT-DC, TNF-DC, and LPS-DC, respectively) for 2 days. Flow cytometric analysis showed that HOT stimulated DC to express the surface maturation markers CD80, CD83, and CD86 dose-dependently and that the up-regulation level was identical to TNF-alpha and LPS. The antigen-uptake capacity of HOT-DC was determined by FITC-labeled albumin uptake. HOT-DC lost albumin uptake capacity comparable to LPS-DC, indicating DC maturity. IL-12 (p70) production by HOT-DC and TNF-DC was not increased in comparison with LPS-DC. The antigen-presenting capacity of HOT-DC as analyzed by allogeneic T cell proliferation was significantly increased in comparison with immature DC and was identical to LPS-DC. These results demonstrate that HOT stimulates DC maturation as well as the other known maturation factors, despite low IL-12 production, and suggests the possibility that DC maturation by HOT can play an important role in the improvement of the immunoregulatory function in patients with impaired host defense.

Adult↗

PubMed2004

Increased frequency of CD27- (naive) B cells and their phenotypic alteration in HIV type 1-infected patients.

To investigate HIV-1-related B cell disorders, the quantity of peripheral CD27 negative (CD27-) B cells, their CD38, CD95, and bcl-2 intensities, and their apoptosis susceptibility were examined by flow cytometry analysis in 16 drug-naive patients, 27 HAART-treated patients, and 20 uninfected controls. CD27- B cells have been recognized as naive B cells. The mean percentage of CD27- B cells was significantly higher in drugnaive patients (88.1%) and in HAART-treated patients (83.9%) than in controls (68.6%) (p < 0.01). The intensities of CD38 and CD95 on CD27- B cells were significantly higher in drug-naive patients than in controls (p < 0.01). The intensity of CD95 on CD27- B cells in HAART-treated patients was lower than that of drug-naive patients, but significantly higher than that of controls (p < 0.01). The intensity of bcl-2 on CD27- B cells in drug-naive patients was lower than that of controls. In drug-naive patients, CD27-B cells with high CD38 expression represented low bcl-2 expression. The CD27- B cells of drug-naive patients showed an increased susceptibility to apoptosis, characterized by diminished cell size and a high frequency of annexin-V binding, compared with controls and HAART-treated patients. These findings suggested that HIV-1 infection affects peripheral CD27- (naive) B cells as well as CD27+ (memory) B cells and that CD27- B cells might be activated and rendered highly susceptible to apoptosis by HIV-1 infection. Some phenotypic alterations in CD27- B cells may continue after the reduction of HIV-1 loads by effective antiviral therapy.

ADP-ribosyl Cyclase↗

PubMed2004

Selective CD27+ (memory) B cell reduction and characteristic B cell alteration in drug-naive and HAART-treated HIV type 1-infected patients.

To investigate HIV-1-related B cell disorders, the quantity of CD27 positive (CD27+) B cells and their CD38, CD95, and bcl-2 intensities were examined by flow cytometry analysis in 16 drug-naive patients, 27 highly active antiretroviral therapy (HAART)-treated patients, and 20 uninfected controls. CD27+ B cells have been recognized as memory B cells. The mean percentage of CD27+ B cells was significantly lower in drug-naive patients (11.9%) and in HAART-treated patients (16.1%) than in controls (31.4%) (p < 0.01). The intensities of CD38 and CD95 on CD27+ B cells were higher in drug-naive patients than in controls (p < 0.01 in CD95). The intensity of CD95 on CD27+ B cells in HAART-treated patients was lower than that of drug-naive patients, but significantly higher than that of controls (p < 0.01). The intensity of bcl-2 on CD27+ B cells was equivalent among the three groups. These findings suggest that disturbance of peripheral B cell composition, exemplified by CD27+ B cell reduction, exists in both drug-naive and HAART-treated HIV-1-infected patients. In addition, the augmented apoptotic state of CD27+ B cells found in HAART-treated patients with undetectable viral loads, indicated by CD95 elevation, suggests that some HIV-1-related B cell disorders last for years after effective antiviral therapy.

ADP-ribosyl Cyclase↗

PubMed2003

A patient in whom only hepatitis B virus (HBV) was thought to have been contracted, by kissing, from a same-sex partner coinfected with HBV and human immunodeficiency virus-1.

A 31-year-old homosexual man was admitted to our hospital in August 2001 with liver dysfunction. His diagnosis was acute hepatitis B. He had had a steady partner coinfected with hepatitis B virus (HBV) and human immunodeficiency virus-1 (HIV) from August 2000 to July 2001. Because he knew that the partner was infected with HIV, the sexual relationship had included only deep kissing, with no oral-genital or anal-genital sex. The serum HBV DNA level of the partner was relatively high compared with the serum HIV RNA level. Direct sequencing of the full HBV DNA genome from serum showed that the entire base sequences of the viruses from both patients were of genotype A and identical. HBV infectivity was shown to be stronger than that of HIV in our patient, in whom only HBV was transmitted from a partner coinfected with HBV and HIV. This case highlights the importance of HBV as a sexually transmitted disease.

Acute Disease↗

PubMed2003

[Evaluation of an immunochromatography test kit for rapid diagnosis of influenza].

We assessed the sensitivity and specificity of the Capilia Flu AB rapid diagnosis kit for influenza that utilizes the immunochromatography method. Tested were 114 influenza like illness patients in the 2001/2002 influenza season. We used Capilia Flu AB and Infu A . B Quick, a rapid diagnosis kit based on enzyme immunoassay. As laboratory confirmation tests, influenza virus isolation and polymerase chain reaction (PCR) were done. Those patients with positive results from virus isolation or PCR were regarded as influenza patients. The sensitivities of nasal swab, pharyngeal swab, and nasal wash specimens were 82.8%, 80.0%, and 75.0%, respectively. The specificities of nasal swab, pharyngeal swab, and nasal wash specimens were 95.3%, 93.9%, and 100%, respectively. A total of 20 patients displayed different results in comparison of their nasal and pharyngeal swabs: 15 patients were positive with the nasal swab but negative with the pharyngeal swab and 5 patients were negative with the nasal swab but positive with the pharyngeal swab. Nasal swab would seem to be preferable in terms of sensitivity. The sensitivity and specificity of Capilia Flu AB were a little higher than those of Influ A . B Quick, but with no significant difference. The one-step operation of Capilia Flu AB is easier than the four steps required by Influ A . B Quick, but the time required to make a diagnosis is the same. No significant age related difference in the effectiveness of the kits was found. The Capilia Flu AB rapid diagnosis kit is useful in clinical practice because it has good sensitivity (about 80%) and specificity (about 90%), and it is easy to use.

Adolescent↗

PubMed2003

Poorly differentiated adenocarcinoma with signet-ring cells of the Vater's ampulla, without jaundice but with disseminated carcinomatosis.

A 49-year-old man was hospitalized because of a 2-month history of purpura in his extremities and for back pain. Laboratory findings showed alkaline phosphatase to be greatly elevated, and platelet counts and coagulation factor showed that the patient had disseminated intravascular coagulation (DIC). Compression fractures of the thoracic vertebrae were found on radiological examination. The histological findings from bone marrow showed metastasis of adenocarcinoma with signet-ring cells, although the primary site was unknown. To reduce tumor cells in number and improve DIC, 11 cycles of 5-Fluorouracil and leucovorin therapy were done, and the patient survived for 12 months. Autopsy showed a 0.8 cm diameter, poorly differentiated adenocarcinoma with the signet-ring cell type in the lamina propria of the Vater's ampulla. Many metastatic foci and micro tumor emboli were found in the lung and in bone marrow. The sections of the stomach, the gallbladder, urinary bladder, prostate, and thyroid gland showed no malignant cells. These findings suggest that the origin of the cancer may have been located in the Vater's ampulla. This is a rare case of an ampullary tumor of poorly differentiated adenocarcinoma with the signet-ring cell type, without jaundice but with multiple metastasis. 5-Fluorouracil and leucovorin were effective for increasing survival time and improving quality of life.

Ampulla of Vater↗

PubMed2002

Increased frequency of IFN-gamma-producing peripheral CD8+ T cells with memory-phenotype in patients with chronic hepatitis C.

To identify the capacity for cytokine production and the phenotypic characteristics of peripheral CD8(+) T cells in patients with chronic hepatitis C, 31 patients with chronic hepatitis C and 22 healthy controls were studied at the single cell level by three-color flow cytometry. Whole blood was stained with surface CD8, intracellular interferon-gamma (IFN-gamma), and interleukin-4 (IL-4), surface CD8, CD28, and intracellular IFN-gamma after stimulation with PMA plus ionomycin, and then surface CD8, CD45RA, and CD28. IFN-gamma-producing peripheral CD8(+) T cells were found frequently in patients than in controls (P < 0.05), whereas IL-4-producing peripheral CD8(+) T cells were not. Although the frequency of peripheral CD28(+)CD8(+) and CD28(-)CD8(+) T cells in patients was not different from that of controls, CD28(+)CD8(+) T cells exceeded CD28(-)CD8(+) T cells in the capacity for IFN-gamma-production after mitogenic stimulation (P < 0.01). In a more detailed analysis of the CD28(+)CD8(+) T cells, CD45RA(-)CD28(+)CD8(+) T cells, defined phenotypically as memory cells, were found frequently in patients than in controls (P < 0.05). There were no significant correlations between the frequency of IFN-gamma-producing peripheral CD8(+) T cells and hepatitis C virus RNA level or serum alanine aminotransferase level in patients. These data suggest that functionally T cytotoxic type 1 and memory CD8(+) T cells are predominant in the peripheral blood of chronic hepatitis C patients and that such activated CD8(+) T cells are associated with liver damage.

Adult↗

PubMed2002

A patient with primary human immunodeficiency virus infection for whom highly active antiretroviral therapy was successful.

We report the case of a 25-year-old male Japanese homosexual with primary human immunodeficiency virus (HIV)-1 infection and early stage syphilis. Approximately 60 days after HIV exposure by sex with another man, the patient abruptly had high fever, after which he experienced a variety of severe, prolonged symptoms such as painful oral mucosa ulcerations, rash, lymphadenopathy, splenomegaly, and a 5.5-kg weight loss. Serum lactate dehydrogenase and liver biochemical test values were elevated. Antibodies to HIV by both enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) test were negative at the time of symptom onset, but serum HIV-1 RNA level was 1 585 000 copies/ml. Antibody seroconversions were found on day 9 after the onset of symptoms by ELISA and on day 16 by WB test, suggesting primary HIV infection. Within 2 weeks of starting highly active antiretroviral therapy (HAART), all symptoms except lymphadenopathy were resolved, and the serum HIV-1 RNA level dramatically decreased to 5011 copies/ml, eventually becoming undetectable by the standard method. The patient has remained asymptomatic for the 18 months since symptom resolution after HAART, and HIV-1 RNA remains undetectable.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Two V(H)5 family genes expressed by human peripheral B cells display differential mutational frequencies in the V(H) region.

The heavy chain variable segment gene (V(H))5 family, one of the seven immunoglobulin (Ig) V(H) families, contains two functional genes, VH251 and VH32. To investigate functional differences between these V(H)5 family genes, V(H) segments expressed by human peripheral B cells were sequenced and analyzed. One hundred fifty-three sequences with unique V(H)DJ(H) recombinations were obtained from 17 adults. The mutational frequency of VH32 derived sequences (6.4%) was higher than that of VH251 derived sequences (4.4%), resulting in a significant difference (P<0.01). Significant differences in mutational frequencies between VH251 and VH32 derived sequences were observed in CDRs and FRs. No significant differences were found in CDR3 length distribution, D segment usage, or J(H) segment usage between VH251 and VH32 derived sequences. These results suggest that mutational frequency is affected, in part, by V(H) gene structure. The difference may occur after recombinational events in B cell development.

Adult↗