Abnormal bone marrow B-cell differentiation in pre-B lymphoma-prone SL/Kh mice

Area of Science:

• Immunology
• Hematology
• Oncology

Background:

• SL/Kh mice develop pre-B lymphomas with specific surface markers.
• These lymphomas show rearranged immunoglobulin heavy chains but germline light chains.
• Pre-lymphoma bone marrow in SL/Kh mice displays an abnormal expansion of BP-1+ pre-B cells.

Purpose of the Study:

• To investigate the cause of the multiclonal expansion of BP-1+ pre-B cells in SL/Kh mice.
• To determine if this expansion is a heritable trait and its genetic basis.
• To ascertain whether the expansion originates from bone marrow stem cells or the microenvironment.

Main Methods:

• Flow cytometry to analyze cell surface phenotypes (B220, BP-1, Thy-1, c-kit, surface immunoglobulin).
• Genetic crosses (F1 hybrids) to assess the heritability of the BP-1+ cell expansion.
• Radiation chimera experiments (SL/Kh --> BALB/c and BALB/c --> SL/Kh) to differentiate stem cell versus microenvironment contributions.

Main Results:

• SL/Kh mice show a significant expansion of BP-1+ pre-B cells (34.8%) compared to other strains (8%).
• This expansion is a dominant heritable trait in F1 hybrids of SL/Kh and NFS/N mice.
• The expansion is independent of endogenous ecotropic virus expression.
• Radiation chimeras demonstrated that the expansion is a property of SL/Kh stem cells, not the bone marrow microenvironment.

Conclusions:

• The multiclonal expansion of BP-1+ pre-B cells in SL/Kh mice is a dominant, heritable characteristic.
• This expansion originates from SL/Kh hematopoietic stem cells.
• These findings identify a critical cellular defect in SL/Kh mice that contributes to their spontaneous pre-B lymphoma development.