Bone marrow chimera

By Levi Clancy for Student Reader on
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Bone marrow chimeras (aka bm chimeras) are mice which have been irradiated, thus killing their bone marrow and all bone marrow derived cells (lymphocytes) and then given bone marrow from another mouse.

T cells from bone marrow chimeras do not react to the donor haplotype, and do react to the recipient haplotype (due to thymic selection) until the self-reactive self are eliminated in the periphery. Class II APCs from bone marrow chimeras will be of the donor haplotype and Class I APCs from bone marrow chimeras will be of the recipient haplotype.

Bone marrow chimeras tolerate skin grafts of the donor haplotype (negative selection) and recipient haplotype (peripheral tolerance); if there is disparity at just one Class I locus there will be slow rejection -- study the steps below to better understand skin graft rejection.

If you are asked whether B cells in a bone marrow chimera can respond to an extracellular bacterial infection
  1. Are the donor and recipient IA alleles the same?

  2. Are the donor and recipient IE alleles the same?

  • If the answer to both questions is yes
    B cells can respond in a thymus-dependent pathway since APCs, TH cells and B cells all share the same Class II MHC alleles. APCs bind and activate the TH cells, which then recognize and activate B cells. Also, B cells can respond in a thymus-independent pathway.

  • If the answer to one question is yes
    B cells can respond in a thymus-dependent pathway since some APCs, TH cells and B cells will have one Class II MHC allele in common (although response will be weaker than above). APCs bind and activate the TH cells, which then recognize and activate B cells. Also, B cells can respond in a thymus-independent pathway.

  • If the answer to neither question is yes
    B cells will respond to the bacterial infection only in a thymus-independent manner because no APCs can present antigens to the T cells, which are not positively selected to interact with the B cell Class II MHC.

If you are asked whether a bone marrow chimera can respond to an intracellular bacterial or viral infection
  1. Are the donor and recipient IA alleles the same?

  2. Are the donor and recipient IE alleles the same?

  1. If the answer to either question is yes
    TH cells will be activated by APCs showing foreign antigens, marking the APC for lysis by CTLs, allowing the TH cells to them activate B cells and leading to both B and T cell memory. More donor and recipient Class II allele overlap increases TH help.

  2. If the answer to neither question is yes
    The CTLs will not be activated by infected cells since there will be no positive selection for the MHC molecules present on APCs.

  1. Are the donor and recipient K alleles the same?

  2. Are the donor and recipient D alleles the same?

  3. Are the donor and recipient L alleles the same?

  • If the answer to three questions is yes
    CTLs will be able to recognize and kill infected cells due to the Class I MHC match.

  • If the answer to two or one questions is yes
    CTLs will be able to recognize and kill infected cells due to the Class I MHC match, although slightly slower than if all Class I alleles matched.

  • If the answer to none of the questions is yes
    No functional CTL response. Bone-marrow derived cells cannot will not be killed, since their Class I MHC haplotype does not match the recipient Class I MHC haplotype at any alleles.

When analyzing proliferation of a bone-marrow chimera responder against a stimulator

Chimera T cells are negatively selected in thymus to not respond to donor Class II haplotype (spell it out, IA?IE?), and peripheral tolerance prevents reactivity to recipient Class II haplotype (again, spell it out IA?IE?). The stimulator is different from none/one/two of the tolerated alleles, leading to none/weak/strong proliferation.

  1. Is the stimulator IA (Class II) allele the same as either of the recipient or donor IA alleles?

  2. Is the stimulator IE (Class II) allele the same as either of the recipient or donor IE alleles?

  • If the answer to both questions is yes
    Zero T cell proliferation.

  • If the answer to one of these questions is yes
    Some T cell proliferation.

  • If the answer to none of these questions is yes
    Strong T cell proliferation.

When analyzing cytotoxicity of a bone-marrow chimera responder against a stimulator

Chimera T cells are negatively selected in thymus to not respond to donor Class I haplotype (spell it out, K?D?L?), and peripheral tolerance prevents reactivity to recipient Class I haplotype (again, spell it out K?D?L?). The stimulator is different from none/one/two/three of the tolerated alleles, leading to none/weak/more/strong cytotoxicity (cell lysis).

  1. Is the stimulator K (Class I) allele the same as either of the recipient or donor K alleles?

  2. Is the stimulator D (Class I) allele the same as either of the recipient or donor D alleles?

  3. Is the stimulator L (Class I) allele the same as either of the recipient or donor L alleles?

  • If all the answer to all of these questions is yes
    No cytotoxicity.

  • If the answer to two of these questions is yes
    Some cytotoxicity.

  • If the answer to one of these questions is yes
    More cytotoxicity.

  • If the answer to none of these questions is yes
    Strong cytotoxicity.