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    Antibodies specific for isotype specific domains of human IgM and human IgG expressed or the B cell surface
    1.
    发明授权
    Antibodies specific for isotype specific domains of human IgM and human IgG expressed or the B cell surface 失效
    对人IgM和人IgG表达的同种型特异性结构域或B细胞表面特异的抗体

    公开(公告)号：US5298420A

    公开(公告)日：1994-03-29

    申请号：US902449

    申请日：1992-06-19

    申请人： Tse W. Chang

    发明人： Tse W. Chang

    IPC分类号： A61K38/00 ,  C07K16/42 ,  C12P21/08 ,  C07K15/28 ,  C12N1/21 ,  C12N5/12

    CPC分类号： C07K16/4283 ,  A61K38/00

    摘要： Membrane anchoring peptides are attached to the C terminal end of the heavy chain of the various immunoglobulin isotypes (IgM, IgD, IgA, IgE, or IgG). The membrane anchoring peptides span the cell membrane lipid bilayer of B cells thereby affixing the associated immunoglobulin to the cell membrane surface. The extracellular segments of these peptides are unique for different isotypes. Epitopes unique to the B cells which produce each isotype are formed, in whole or in part, by these extracellular segments. These membrane-bound immunoglobulin isotype-specific ("migis") extracellular epitopes are not present on the secreted, soluble form of the immunoglobulins, which are not bound to the cell surface by the membrane anchoring peptides. The antibodies of the invention (and other related products) specifically bind to the extracellular migis epitopes of human .mu. chain, human .delta. chain, or human .gamma. chain. The B cells which express the isotypes IgM, IgD or IgG are labeled for destruction when bound by such antibodies or products, and can be destroyed by the cytolytic or regulatory mechanisms of the immune system in order to cause immunosuppression.

    摘要翻译： 膜锚定肽连接到各种免疫球蛋白同种型（IgM，IgD，IgA，IgE或IgG）的重链的C末端。 膜锚定肽跨越B细胞的细胞膜脂质双层，从而将相关的免疫球蛋白附着于细胞膜表面。 这些肽的细胞外区段对于不同的同种型是独特的。 通过这些细胞外片段整体或部分形成产生每个同种型的B细胞特有的表位。 这些膜结合的免疫球蛋白同种型特异性（“migis”）细胞外表位不存在于分泌的可溶形式的免疫球蛋白，其通过膜锚定肽不结合细胞表面。 本发明的抗体（和其它相关产品）特异性结合人（my）链，人（delta）链或人（γ）链的细胞外迁移表位。 表达同种型IgM，IgD或IgG的B细胞在被这些抗体或产物结合时被标记为破坏，并且可以被免疫系统的细胞溶解或调节机制破坏以引起免疫抑制。

    Treating B cell lymphoma or leukemia by targeting specific epitopes on B cell bound immunoglobulins
    7.
    发明授权
    Treating B cell lymphoma or leukemia by targeting specific epitopes on B cell bound immunoglobulins 失效
    通过靶向B细胞结合的免疫球蛋白上的特异性表位来治疗B细胞淋巴瘤或白血病

    公开(公告)号：US5281699A

    公开(公告)日：1994-01-25

    申请号：US531787

    申请日：1990-06-01

    申请人： Tse W. Chang

    发明人： Tse W. Chang

    IPC分类号： A61K38/00 ,  C07K16/06 ,  C07K16/30 ,  A61K37/02 ,  C07K7/08 ,  C07K7/10

    CPC分类号： C07K16/065 ,  C07K16/30 ,  A61K38/00 ,  C07K2317/34

    摘要： Membrane anchoring peptides which are part of the heavy chain of an associated immunoglobulin (IgM, IgD, IgA, IgE, or IgG), span the cell membrane lipid bilayer of B cells thereby affixing the associated immunoglobulin to the cell membrane surface. The extracellular segments of these peptides are unique for different isotypes, but tend to be very similar among different subclasses of a particular isotype. The extracellular segments form in whole or in part an epitope unique to the B cells which produce each isotype. These membrane-bound immunoglobulin isotype-specific ("migis") extracellular epitopes are not present on the secreted, soluble form of the immunoglobulins, which are not bound to the cell surface by the membrane anchoring peptides. The antibodies of the invention (and other related products) bind the extracellular migis epitopes. Tumorous B cells which produce particular isotypes, whether associated with B cell lymphoma and B cell leukemia, can be destroyed when they are bound by such an antibody (or by a derivative product of such an antibody), by any of a number of well-known mechanisms.

    摘要翻译： 作为相关免疫球蛋白（IgM，IgD，IgA，IgE或IgG）重链的一部分的膜锚定肽跨越B细胞的细胞膜脂质双层，从而将相关免疫球蛋白附着于细胞膜表面。 这些肽的细胞外区段对于不同的同种型是独特的，但在特定同种型的不同亚类之间往往是非常相似的。 全部或部分细胞外节段形成产生每个同种型的B细胞特有的表位。 这些膜结合的免疫球蛋白同种型特异性（“migis”）细胞外表位不存在于分泌的可溶形式的免疫球蛋白，其通过膜锚定肽不结合细胞表面。 本发明的抗体（和其他相关产物）结合细胞外migis表位。 产生特定同种型的肿瘤B细胞，无论是否与B细胞淋巴瘤和B细胞白血病相关，当它们被这样的抗体（或通过这种抗体的衍生产物）结合时，可以被破坏， 已知的机制。

    Selecting low frequency antigen-specific single B lymphocytes with correction for background noise
    8.
    发明授权
    Selecting low frequency antigen-specific single B lymphocytes with correction for background noise 失效

    公开(公告)号：US5256542A

    公开(公告)日：1993-10-26

    申请号：US905040

    申请日：1992-06-26

    申请人： Tse W. Chang

    发明人： Tse W. Chang

    IPC分类号： G01N33/50 ,  G01N33/569 ,  G01N21/64 ,  G01N33/536 ,  G01N33/58

    CPC分类号： G01N33/5094 ,  G01N33/56972 ,  Y10S435/808 ,  Y10S435/962 ,  Y10S436/80

    摘要： Disclosed are immunofluorescence staining methods which increase the likelihood that antibodies expressed by a single B cell selected and sorted by fluorescence activated cell sorting are specific for the antigen of interest, and which also allow selection of B cells expressing antibodies of high affinity for the antigen of interest. The antigen-specific single B cells are to be used in a procedure which amplifies and selects their V.sub.H and V.sub.L sequences. The selection for B cells expressing antibodies to specific antigens is increased by labeling B cells with at least two antigen probes, where each antigen probe includes the antigen of interest and the difference between the two probes is that each is labeled with a different fluorochrome. The positive selection achieved using antigen probes with two different colors is preferably combined with a negative selection step, in which autofluorescent cells and sticky cells exhibiting fluorescence for the third irrelevant surface marker are excluded out. The specificity of sorting of the desired B cells can be further enhanced by staining those antigen-specific B cells which produce the immunoglobulin isotype (typically IgG), with targeting molecules reactive with a B cell marker, such as .gamma. chain and CD19, that are conjugated with a different fluorochrome. Thus, the antigen-specific IgG-producing B cells of interest may be labeled with these unique reagents in four color FACS (including one for negative selection), which can sort the desired antigen-specific B cells at enhanced proportions. The differences in relative intensities between the antigen labels and the isotype labels (e.g., IgG labels) among the different antibodies of the single cells selected can be used to determine the relative antigen binding affinity of those antibodies. For example, the ratio of antigen label to IgG label can be calculated for each labeled B cell. The higher the ratio, the higher the relative affinity of the antibodies on the B cells for the antigen. After sorting the B cells with FACS, those B cells with high affinity are preferred for analysis by the single cell-PCR procedure to amplify and clone the V.sub.H and V.sub.L segments of interest.

    Selecting low frequency antigen-specific single B lymphocytes
    9.
    发明授权
    Selecting low frequency antigen-specific single B lymphocytes 失效
    选择低频抗原特异性单一B淋巴细胞

    公开(公告)号：US5326696A

    公开(公告)日：1994-07-05

    申请号：US21619

    申请日：1993-02-17

    申请人： Tse W. Chang

    发明人： Tse W. Chang

    IPC分类号： G01N33/50 ,  G01N33/569 ,  G01N33/533 ,  G01N21/64 ,  G01N33/536

    CPC分类号： G01N33/5094 ,  G01N33/56972 ,  Y10S435/808 ,  Y10S435/962 ,  Y10S436/80

    摘要： Disclosed are immunofluorescence staining methods which increase the likelihood that antibodies expressed by a single B cell selected and sorted by fluorescence activated cell sorting are specific for the antigen of interest, and which also allow selection of B cells expressing antibodies of high affinity for the antigen of interest. The selection for B cells expressing antibodies to specific antigens is increased by labeling B cells with at least two antigen probes, where each antigen probe includes the antigen of interest and is labeled with a different fluorochrome. The positive selection is preferably combined with a negative selection step, in which autofluorescent cells and sticky cells are excluded out. The specificity of sorting of the desired B cells can be further enhanced by staining those antigen-specific B cells which produce the immunoglobulin isotype (typically IgG), with targeting molecules reactive with a B cell marker, such as .gamma. chain and CD19, that are conjugated with a different fluorochrome. Thus, the antigen-specific IgG-producing B cells of interest may be labeled with these unique reagents in four color FACS (including one for negative selection), which can sort the desired antigen-specific B cells at enhanced proportions. After sorting the B cells with FACS, those B cells with high affinity are preferred for analysis by the single cell-PCR procedure to amplify and clone the V.sub.H and V.sub.L segments of interest.

    摘要翻译： 公开了免疫荧光染色方法，其增加了通过荧光激活细胞分选选择和分选的单个B细胞表达的抗体对感兴趣的抗原特异的可能性，并且还允许选择表达对亲和素抗原具有高亲和力的抗体的B细胞 利益。 通过用至少两个抗原探针标记B细胞来增加表达针对特异性抗原的抗体的B细胞的选择，其中每个抗原探针包括感兴趣的抗原并用不同的荧光染料标记。 阳性选择优选与否定选择步骤组合，其中自发荧光细胞和粘性细胞被排除。 通过染色产生免疫球蛋白同种型（通常为IgG）的那些抗原特异性B细胞，可以进一步增强所需B细胞的分选的特异性，其中靶向分子与B细胞标记如γ链和CD19反应，其为 与不同的荧光染料缀合。 因此，可以用四色FACS（包括一种用于阴性选择）的这些独特的试剂来标记感兴趣的抗原特异性IgG产生B细胞，其可以以更高的比例对所需的抗原特异性B细胞进行分类。 在用FACS分选B细胞后，优选用亲和力高的B细胞通过单细胞PCR方法进行分析，以扩增和克隆感兴趣的VH和VL片段。